2021/12/16 更新

写真a

キム ヘスク
金 惠淑
KIM Hye-Sook
所属
医歯薬学域 准教授
職名
准教授
外部リンク

学位

  • 博士(薬学)

研究キーワード

  • 細胞生物学

  • 医薬品開発学

  • マラリア学

  • 感染症治療学

  • 微生物学

研究分野

  • ライフサイエンス / 寄生虫学

  • ライフサイエンス / 薬系衛生、生物化学

  • ライフサイエンス / 環境、天然医薬資源学

学歴

  • 岡山大学   The Graduate School of Natural Science and Technology  

    1995年4月 - 1998年3月

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    国名: 日本国

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  • 岡山大学   Graduate School of Pharmaceutical Sciences  

    1993年4月 - 1995年3月

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    国名: 日本国

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経歴

  • 岡山大学   大学院医歯薬学総合研究科   准教授

    2002年6月 - 現在

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  • 岡山大学   大学院自然科学研究科   講師

    1999年12月 - 2002年5月

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  • 岡山大学   大学院自然科学研究科   助手

    1999年4月 - 1999年11月

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  • 独立行政法人日本学術振興会   外国人特別研究員(岡山大学)

    1998年4月 - 1999年3月

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    国名:日本国

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論文

  • A trial for a diagnosis of tertian malaria recently reemerging in the Republic of Korea using microtiter plate hybridization assay 査読

    Am. J Trop. Med. Hyg,   63 ( 1 )   80 - 84   2000年7月

  • Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosis. 査読 国際誌

    Akira Sato, Akihiro Yamamoto, Akira Shimotsuma, Yoko Ogino, Naoki Funayama, Yui Takahashi, Akiko Hiramoto, Yusuke Wataya, Hye-Sook Kim

    FEBS open bio   10 ( 11 )   2417 - 2426   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    MicroRNAs (miRNAs) are small noncoding RNA molecules that interact with target mRNAs at specific sites to induce cleavage of the mRNA or inhibit translation. Such miRNAs play a vital role in gene expression and in several other biological processes, including cell death. We have studied the mechanisms regulating cell death (necrosis in original F28-7 cells and apoptosis in their variant F28-7-A cells) in the mouse mammary tumor cell line FM3A using the anticancer agent floxuridine (FUdR). We previously reported that inhibition of heat-shock protein 90 by the specific inhibitor geldanamycin (GA) in F28-7 cells causes a shift from necrosis to apoptosis. In this study, we investigated the intracellular miRNA expression profiles of FUdR-treated F28-7 cells (necrotic condition), GA plus FUdR-treated F28-7 cells (apoptotic condition), and FUdR-treated F28-7-A cells (apoptotic condition) through miRNA microarray analysis. In addition, we knocked down Dicer, a key molecule for the expression of mature miRNAs, in F28-7 cells to examine whether it modulates FUdR-induced cell death. Our analysis revealed that the miRNA expression patterns differ significantly between these cell death conditions. Furthermore, we identified miRNA candidates that regulate cell death. Knockdown of Dicer in FUdR-treated necrosis-fated cells caused a partial shift from necrosis to apoptosis. These findings suggest that modulation of miRNA expression patterns influences the decision of cell death fate toward necrosis or apoptosis. Our findings may serve as a basis for further study of the functions of miRNAs in cell death mechanisms.

    DOI: 10.1002/2211-5463.12995

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  • Anticancer Strategy Targeting Cell Death Regulators: Switching the Mechanism of Anticancer Floxuridine-Induced Cell Death from Necrosis to Apoptosis. 査読 国際誌

    Akira Sato, Akiko Hiramoto, Hye-Sook Kim, Yusuke Wataya

    International journal of molecular sciences   21 ( 16 )   2020年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cell death can be broadly characterized as either necrosis or apoptosis, depending on the morphological and biochemical features of the cell itself. We have previously reported that the treatment of mouse mammary carcinoma FM3A cells with the anticancer drug floxuridine (FUdR) induces necrosis in the original clone F28-7 but apoptosis in the variant F28-7-A. We have identified regulators, including heat shock protein 90, lamin-B1, cytokeratin-19, and activating transcription factor 3, of cell death mechanisms by using comprehensive gene and protein expression analyses and a phenotype-screening approach. We also observed that the individual inhibition or knockdown of the identified regulators in F28-7 results in a shift from necrotic to apoptotic morphology. Furthermore, we investigated microRNA (miRNA, miR) expression profiles in sister cell strains F28-7 and F28-7-A using miRNA microarray analyses. We found that several unique miRNAs, miR-351-5p and miR-743a-3p, were expressed at higher levels in F28-7-A than in F28-7. Higher expression of these miRNAs in F28-7 induced by transfecting miR mimics resulted in a switch in the mode of cell death from necrosis to apoptosis. Our findings suggest that the identified cell death regulators may play key roles in the decision of cell death mechanism: necrosis or apoptosis.

    DOI: 10.3390/ijms21165876

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  • Direct interaction analysis of microRNA-351-5p and nuclear scaffold lamin B1 mRNA by the cell-free in vitro mRNA/miRNA binding evaluation system. 査読 国際誌

    Akira Sato, Yoko Ogino, Akira Shimotsuma, Akiko Hiramoto, Hye-Sook Kim, Yusuke Wataya

    Nucleosides, nucleotides & nucleic acids   1 - 7   2020年1月

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    記述言語:英語  

    We previously demonstrated that miR-351-5p regulates nuclear scaffold lamin B1 expression and mediates the anticancer floxuridine-induced necrosis shift to apoptosis in mammalian tumor cells. Notably, it is unknown whether lamin B1 mRNA is a direct target of miR-351-5p. Here, we show that miR-351-5p interacts with a lamin B1 mRNA partial sequence by using the cell-free in vitro miRNA and mRNA binding evaluation system. In addition, the interaction of miR-351-5p/lamin B1 mRNA was suppressed by an miR-351-5p inhibitor. Our findings are important in exploring the functions of miRNAs in cellular processes, including cell death.

    DOI: 10.1080/15257770.2019.1702675

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  • Pharmacokinetic analysis of new synthetic antimalarial N-251 査読

    Kazuaki Okada, Akira Sato, Akiko Hiramoto, Rena Isogawa, Yuji Kurosaki, Kazutaka Higaki, Shin-Ichi Miyoshi, Kyung-Soo Chang, Hye-Sook Kim

    Tropical Medicine and Health   47 ( 1 )   2019年12月

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    担当区分:責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1186/s41182-019-0167-4

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    その他リンク: http://link.springer.com/article/10.1186/s41182-019-0167-4/fulltext.html

  • Genomic and biological features of Plasmodium falciparum resistance against antimalarial endoperoxide N-89. 査読 国際誌

    Masayuki Morita, Kosuke Hayashi, Akira Sato, Akiko Hiramoto, Osamu Kaneko, Rena Isogawa, Yuji Kurosaki, Shin-Ichi Miyoshi, Kyung-Soo Chang, Yusuke Wataya, Hye-Sook Kim

    Gene   716   144016 - 144016   2019年10月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Drug resistance of malaria parasites remains a problem affecting antimalarial treatment and control of the disease. We previously synthesized an antimalarial endoperoxide, N-89, having high antimalarial effects in vitro and in vivo. In this study we seek to understand the resistant mechanism against N-89 by establishing a highly N-89-resistant clone, named NRC10H, of the Plasmodium falciparum FCR-3 strain. We describe gene mutations in the parent FCR-3 strain and the NRC10H clone using whole-genome sequencing and subsequently by expression profiling using quantitative real-time PCR. Seven genes related to drug resistance, proteolysis, glycophosphatidylinositol anchor biosynthesis, and phosphatidylethanolamine biosynthesis exhibited a single amino acid substitution in the NRC10H clone. Among these seven genes, the multidrug resistance protein 2 (mdr2) variant A532S was found only in NRC10H. The genetic status of the P. falciparum endoplasmic reticulum-resident calcium binding protein (PfERC), a potential target of N-89, was similar between the NRC10H clone and the parent FCR-3 strain. These findings suggest that the genetic alterations of the identified seven genes, in particular mdr2, in NRC10H could give rise to resistance of the antimalarial endoperoxide N-89.

    DOI: 10.1016/j.gene.2019.144016

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  • Oral activity of the antimalarial endoperoxide 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against Leishmania donovani complex 査読

    Kofi Dadzie Kwofie, Kai Sato, Chizu Sanjoba, Akina Hino, Rieko Shimogawara, Michael Amoa-Bosompem, Irene Ayi, Daniel A. Boakye, Abraham K. Anang, Kyung-Soo Chang, Mitsuko Ohashi, Hye-Sook Kim, Nobuo Ohta, Yoshitsugu Matsumoto, Shiroh Iwanaga

    PLOS Neglected Tropical Diseases   13 ( 3 )   e0007235 - e0007235   2019年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science (PLoS)  

    DOI: 10.1371/journal.pntd.0007235

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  • Potent Antimalarial Activity of Two Arenes Linked with Triamine Designed To Have Multiple Interactions with Heme. 査読 国際誌

    Yosuke Sakata, Kosuke Yabunaka, Yuko Kobayashi, Hirohisa Omiya, Naoki Umezawa, Hye-Sook Kim, Yusuke Wataya, Yoshimi Tomita, Yosuke Hisamatsu, Nobuki Kato, Hirokazu Yagi, Tadashi Satoh, Koichi Kato, Haruto Ishikawa, Tsunehiko Higuchi

    ACS medicinal chemistry letters   9 ( 10 )   980 - 985   2018年10月

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    記述言語:英語  

    Based on the idea that compounds designed to exhibit high affinity for heme would block hemozoin formation, a critical heme-detoxification process for malarial parasites, we synthesized a series of compounds with two π-conjugated moieties at terminal amino groups of triamine. These compounds exhibited moderate to high antimalarial activities in vitro toward both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. In a P. berghei-infected mouse model, 3a and 12a showed potent antimalarial activities compared to artesunate, as well as a prolonged duration of antimalarial effect. We found a good correlation between protective activity against hemin degradation and antimalarial activity. Compounds 8b and 3a strongly inhibited hemozoin formation catalyzed by heme detoxification protein.

    DOI: 10.1021/acsmedchemlett.8b00222

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  • Multiple antiviral activities of the antimalarial and anti-hepatitis C drug candidates N-89 and N-251. 査読 国際誌

    Ueda Y, Gu W, Dansako H, Kim HS, Yoshizaki S, Okumura N, Ishikawa T, Nishitsuji H, Kato F, Hishiki T, Satoh S, Ishii K, Masuda M, Shimotohno K, Ikeda M, Kato N

    Biochemistry and biophysics reports   15   1 - 6   2018年9月

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  • Potential of synthetic endoperoxides against Trichomonas vaginalis in vitro 査読

    Min-Young Seo, Jae-Sook Ryu, Akira Sato, Yuji Kurosaki, Kyung-Soo Chang, Hye-Sook Kim

    PARASITOLOGY INTERNATIONAL   66 ( 5 )   619 - 621   2017年10月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Metronidazole is well known for medicine against Trichomonas vaginalis infection, but it has side effects though it is effective, and especially because reports of metronidazole-tolerant species are increasing, the development of new medicine is being required. Here, we noticed the killing effects of endoperoxide compounds, N-89 and N-251 as new antimalarial drug candidates, on T. vaginalis and searched the possibility of development of new medicine. We added each of metronidazole, artemisinin, and two of new endoperoxides (N-89 and N-251) to metronidazole-resistant and -sensitive species and compared its anti-trichomonal efficacy. For metronidazole, IC50 value, 50% of killing concentration for T. vaginalis, was very low for metronidazole-sensitive isolates (11.7 to 22.8 mu M), but was high for metronidazole-resistant ones (182.9 to 730.4 mu M). The IC50 values of N-89 and N-251 were 41.0 to 60.0 mu M, and 82.0 to 300.0 mu M for metronidazole-sensitive and-resistant isolates, respectively. In conclusion, we found the endoperoxides, N-89 and N-251, have anti-trichomonal effect against metronidazole-resistant T. vaginalis as well as metronidazole-sensitive ones. These results indicate that the anti-richomonal effects for our endoperoxides are equivalent or better in metronidazole-resistant T. vaginalis in comparison to metronidazole.

    DOI: 10.1016/j.parint.2017.05.008

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  • Role of the uridine/cytidine kinase 2 mutation in cellular sensitiveness toward 3′-ethynylcytidine treatment of human cancer cells 査読

    Akira Sato, Takeshi Takano, Akiko Hiramoto, Tomoharu Naito, Akira Matsuda, Masakazu Fukushima, Yusuke Wataya, Hye Sook Kim

    Anti-Cancer Drugs   28 ( 7 )   781 - 786   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1097/CAD.0000000000000519

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  • Evaluation of preclinical antimalarial drugs, which can overcome direct acting antivirals-resistant hepatitis C viruses, using the viral reporter assay systems 査読

    Youki Ueda, Hiromichi Dansako, Shinya Satoh, Hye-Sook Kim, Yusuke Wataya, Hiroyuki Doi, Masanori Ikeda, Nobuyuki Kato

    VIRUS RESEARCH   235   37 - 48   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a major global health problem. Recently developed treatments with direct-acting antivirals (DAAs) have largely improved the sustained virologic response rate of patients with chronic hepatitis C. However, this approach is still hindered by its great expense and the problem of drug resistance. Using our cell-based HCV assay systems, we reported that the preclinical antimalarial drugs N-89 and N-251 exhibited potent anti-HCV activities. In this study we used our assay systems to evaluate the anti-HCV activities of six kinds of DAAs individually or in combination with N-89 or N-251. The results showed that the DAAs had potent anti-HCV activities and N-89 or N-251 contributed additive or synergistic effect. Using DAA-resistant HCV-RNA-replicating cells, which were prepared by continuous treatment with each DAA, we demonstrated that N-89 and N-251 could overcome all of the DAA-resistant HCVs. These preclinical drugs would have been potential as components of a therapeutic regimen that also included combinations of various DAAs. In addition, sequence analysis of the NS3-NS5B regions of the DAA-resistant HCV genomes newly found several amino acid (aa) substitutions that were suggested to contribute to DAA-resistance in addition to the aa substitutions already known to cause DAA-resistance. Among these new aa substitutions, we found that two substitutions in the NS3 region (D79G and S174Y) contributed to simeprevirand/or asunaprevir-resistance.

    DOI: 10.1016/j.virusres.2017.03.015

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  • Novel synthetic compounds with endoperoxide structure damage juvenile stage of Schistosoma mansoni by targeting lysosome-like organelles

    Masafumi Yamabe, Takashi Kumagai, Rieko Shimogawara, Emmanuel Awusah Blay, Akina Hino, Koichiro Ichimura, Akira Sato, Hye-Sook Kim, Nobuo Ohta

    PARASITOLOGY INTERNATIONAL   66 ( 1 )   917 - 924   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    The new synthetic compound 1,2,6,7-tetraoxaspiro[7.11]nonadecan (N-89), a novel anti-malaria drug candidate, is also a promising drug candidate against schistosomiasis with killing effects against juvenile stage of S. mansoni. In order to investigate how N-89 kills schistosomes, we used a derivative of N-89, 6-(1,2,6,7-tetraoxaspiro[7.11] nonadec-4-yl)hexan-1-ol (N-251), which enables us to conjugate with fluorescent reagents. Firstly, N-251 showed strong killing effects to larvae of S. mansoni in vitro. Ultrastructural analysis showed the disruptions of the lysosome-like organelles or the acetabular glands, followed by cytoplasmic lysis inside the worm body in N-251 -treated group under electron microscopy. For rhodamine-conjugated N-251 and organelle markers, we observed that N-251 accumulated in acidic organelle. In addition, LysoTracker signals in these acidic organelles disappeared in N-251-treated group over time. Finally, we observed that the activity of cathepsin B, a lysosome-specific enzyme, was also decreased together with alternation of acidic organelle marker signal by N-251-treated group. These results suggested that our synthesized compounds induced the dysfunction or the disruption of acidic lysosome-like organelles and finally led to worm death. (C) 2016 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.parint.2016.10.013

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  • In vitro inhibition of Toxoplasma gondii by the anti-malarial candidate, 6-(1,2,6,7-tetraoxaspiro[7.1 1]nonadec-4-yl)hexan-1-ol 査読

    Chun-Feng Xin, Hye-Sook Kim, Akira Sato, Hak-Jae Lee, You-Won Lee, Kyoung-Ho Pyo, Eun-Hee Shin

    PARASITOLOGY INTERNATIONAL   65 ( 5 )   494 - 499   2016年10月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    An anti-malarial candidate, 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-l-ol (N-251), was studied to characterize its potential as a novel anti-Toxoplasma gondii drug. In the present study, IC50 and LC50 of N-251 on host cells and T. gondii were compared to those of artemisinin and sulfadiazine. The IC50 on Huh-7 cells was 10.19 mu g/ml, 67.69 mu g/ml and 310.17 mu g/ml for N-251, artemisinin, and sulfadiazine, respectively. The LC50 for anti-T. gondii effect was shown to be 1.11 mu g/ml, 5.79 mu g/ml, and 5.45 mu g/ml for N-251, artemisinin and sulfadiazine, respectively. N-251 concentration causing complete parasiticidal effect with minimal cytotoxicity on host cells was determined to be 5 mu g/ml. Additionally, the anti-T. gondii effect of N-251 was confirmed by ultrastructural changes, loss of organelles, degenerated morphology and the increase of amylopectin as detected by transmission electron microscope (TEM). Accordingly, the present study suggests that the anti-malarial synthetic endoperoxide, N-251, is an emerging drug candidate more effective than artemisinin and sulfadiazine. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.parint.2016.06.013

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  • MicroRNA-351 Regulates Two-Types of Cell Death, Necrosis and Apoptosis, Induced by 5-fluoro-2'-deoxyuridine

    Akira Sato, Takuya Omi, Akihiro Yamamoto, Akito Satake, Akiko Hiramoto, Mitsuko Masutani, Sei-ichi Tanuma, Yusuke Wataya, Hye-Sook Kim

    PLOS ONE   11 ( 4 )   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Cell-death can be necrosis and apoptosis. We are investigating the mechanisms regulating the cell death that occurs on treatment of mouse cancer cell-line FM3A with antitumor 5-fluoro-2'-deoxyuridine (FUdR): necrosis occurs for the original clone F28-7, and apoptosis for its variant F28-7-A. Here we report that a microRNA (miR-351) regulates the cell death pattern. The miR-351 is expressed strongly in F28-7-A but only weakly in F28-7. Induction of a higher expression of miR-351 in F28-7 by transfecting an miRNA mimic into F28-7 resulted in a change of the death mode; necrosis to apoptosis. Furthermore, transfection of an miR-351 inhibitor into F28-7-A resulted in the morphology change, apoptosis to necrosis, in this death-by-FUdR. Possible mechanism involving lamin B1 in this miR-351's regulatory action is discussed.

    DOI: 10.1371/journal.pone.0153130

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  • New antimalarial endoperoxides for drug-resistant Plasmodium falciparum: The current situation 査読

    Kim H.-S, Katamoto A, Sato A, Wataya Y, Doi H

    Okayama Igakkai Zasshi (Journal of Okayama Medical Association)   127   231 - 235   2015年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Improvement of Oral Bioavailability of N-251, a Novel Antimalarial Drug, by Increasing Lymphatic Transport with Long-Chain Fatty Acid-Based Self-Nanoemulsifying Drug Delivery System

    Chikako Imada, Takuma Takahashi, Makoto Kuramoto, Kazufumi Masuda, Ken-ichi Ogawara, Akira Sato, Yusuke Wataya, Hye-Sook Kim, Kazutaka Higaki

    PHARMACEUTICAL RESEARCH   32 ( 8 )   2595 - 2608   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER/PLENUM PUBLISHERS  

    Purpose The objective of this study was to improve the absorption behavior of N-251, a novel antimalarial drug, by preparing an appropriate self-nanoemulsifying drug delivery system (SNEDDS).
    Methods Two different types of SNEDDS formulations, medium-chain fatty acid-based SNEDDS (MC-SNEDDS) and long-chain fatty acid-based SNEDDS (LC-SNEDDS), were prepared based on pseudo-ternary phase diagram, and examined for their in vivo oral absorption behavior in rats.
    Results Oral dosing of MC-SNEDDS formulations significantly improved the bioavailability (BA) of N-251 compared with N-251 powders. However, its high hepatic extraction limited the BA of N-251 to only 0.49 for MC-SNEDDS B, the best formulation of MC-SNEDDS. LC-SNEDDS formulations, especially LC-SNEDDS F provided the highest BA, 0.65, and successfully attenuated the inter-individual difference in the absorption behavior. Furthermore, it was confirmed that lymphatic transport of N-251 for LC-SNEDDS F was significantly increased up to around 3.19 times larger than that for MC-SNEDDS B. Simulation study suggested that 20 to 39% of N-251 uptaken by the small intestine would be delivered to lymphatic system after oral administration of LC-SNEDDS F.
    Conclusions SNEDDS formulations significantly improved the absorption behavior of N-251 and long-chain fatty acid-based lipid further improved it by avoiding the hepatic first-pass elimination.

    DOI: 10.1007/s11095-015-1646-x

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  • Stage specific activity of synthetic antimalarial endoperoxides, N-89 and N-251, against Plasmodium falciparum 査読

    Masayuki Morita, Takahiko Koyama, Hitomi Sanai, Akira Sato, Akiko Hiramoto, Araki Masuyama, Masatomo Nojima, Yusuke Wataya, Hye-Sook Kim

    PARASITOLOGY INTERNATIONAL   64 ( 1 )   113 - 117   2015年2月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    We have reported that two endoperoxides, N-89 and N-251, synthesized in 2001, possess potent antimalarial activities. Aiming at their eventual use for curing malaria in humans, we have been investigating various aspects of their antimalarial actions. Here we show that N-89 and N-251 inhibit the growth of Plasmodium falciparum within human erythrocytes in vitro at its lifecycle stage 'trophozoite' specifically. It is known that artemisinin compounds, which are currently used for curing malaria, have other stage-specificities. Therefore, it is likely that the antimalarial mechanism of N-89 and N-251 differs from those of artemisinin compounds. As malaria parasites resistant to artemisinin-based combination therapy are currently emerging in some tropical regions, N-89 and N-251 are candidates for overcoming these new problems. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.parint.2014.10.007

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  • Role of activating transcription factor 3 protein ATF3 in necrosis and apoptosis of cell death induced by 5-Fluoro-2′-deoxyuridine

    Sato, A, Nakama, K, Satake, A, Yamamoto, A, Hiramoto, A, Masutani, M, Wataya, Y, Kim, H.-S

    FEBS J   281 ( 7 )   1892 - 1900   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/febs.12752

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  • Molecular dynamics and energetic perceptions of substrate recognition by thymidylate kinase

    Mahmoud Kandeel, Yoshihiro Noguchi, Kentaro Oh-Hashi, Hye-Sook Kim, Yukio Kitade

    JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY   115 ( 3 )   2089 - 2097   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Plasmodium deoxyguanylate pathways are an attractive area of investigation for future metabolic and drug discovery studies due to their unusual substrate specificities. We investigated the energetic contribution to thymidylate kinase substrate binding, and the forces underlying ligand recognition. The binding constant varied from 8 x 10(4) M-1 at 290 K to 6 x 10(4) M-1 at 310 K for dGMP, and from 16 x 10(4) M-1 at 290 K to 4 x 10(4) M-1 at 310 K for TMP. Delta C (p) was estimated as -1.75 kJ mol(-1) K-1 for TMP and +2 kJ mol(-1) K-1 for dGMP. In comparison with TMP, the binding of dGMP to PfTMK produced less favorable enthalpy change, positive or favorable entropic contribution at lower temperature, positive heat capacity change, negative , positive Delta S (other), higher total solvent-exposed surface area and more or less rigid body binding. These changes indicate unfavorable conditions for proper binding and lower conformational changes, and suboptimal structural reordering during dGMP binding.

    DOI: 10.1007/s10973-013-3319-5

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  • New Preclinical Antimalarial Drugs Potently Inhibit Hepatitis C Virus Genotype 1b RNA Replication

    Youki Ueda, Midori Takeda, Kyoko Mori, Hiromichi Dansako, Takaji Wakita, Hye-Sook Kim, Akira Sato, Yusuke Wataya, Masanori Ikeda, Nobuyuki Kato

    PLOS ONE   8 ( 8 )   e72519   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed.
    Methodology/Principal Findings: Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8) were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251) showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-alpha demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-alpha-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-alpha and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect.
    Conclusions/Significance: We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin.

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  • Applications of triphenylpyrylium salt-sensitized electron-transfer photo-oxygenation reactions to the synthesis of benzo-fused 1,4-diaryl-2,3- dioxabicyclo[2.2.2]octanes as new antimalarial cyclic peroxides

    Masaki Kamata, Jun-Ichi Hagiwara, Tomoko Hokari, Chiharu Suzuki, Ryohta Fujino, Sayaka Kobayashi, Hye-Sook Kim, Yusuke Wataya

    Research on Chemical Intermediates   39 ( 1 )   127 - 137   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Benzo-fused 1,4-diaryl-2,3-dioxabicyclo[2.2.2]octanes 4a-d (4a: Ar = C 6H5, 4b: Ar = p-FC6H4, 4c: Ar = p-MeC6H4, 4d: Ar = p-MeOC6H4) were synthesized by 2,4,6-triphenylpyrylium tetrafluoroborate (TPPBF 4)-sensitized photoinduced electron-transfer (PET)-promoted oxygenation reactions, and their in-vitro antimalarial activity was evaluated. The results showed that these substances have sufficiently high activity to enable them to serve as antimalarial lead compounds. In addition, TPPBF 4-biphenyl-cosensitized PET oxygenation was shown to be an efficient method for introduction of an O-O moiety in the construction of antimalarial cyclic peroxides. Graphical Abstract: New antimalarial bicyclic peroxides 4 were synthesized by TPPBF4-sensitized photoinduced electron-transfer oxygenation reactions.[Figure not available: see fulltext.] © 2012 Springer Science+Business Media B.V.

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  • Plasmodium falciparum Endoplasmic Reticulum-Resident Calcium Binding Protein Is a Possible Target of Synthetic Antimalarial Endoperoxides, N-89 and N-251 査読

    Masayuki Morita, Hitomi Sanai, Akiko Hiramoto, Akira Sato, Osamu Hiraoka, Takaya Sakura, Osamu Kaneko, Araki Masuyama, Masatomo Nojima, Yusuke Wataya, Hye-Sook Kim

    JOURNAL OF PROTEOME RESEARCH   11 ( 12 )   5704 - 5711   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    The endoperoxide artemisinin is a current first-line antimalarial and a critical component of the artemisinin-based combination therapies (ACT) recommended by WHO for treatment of Plasmodium falciparum, the deadliest of malaria parasites. However, recent emergence of the artemisinin-resistant P. falciparum urged us to develop new antimalarial drugs. We have shown that synthetic endoperoxides N-89 and its hydroxyl derivative N-251 had high antimalarial activities both in vivo and in vitro. However, the mechanisms including the cellular targets of the endoperoxide antimalarials are not well understood. Thus, in this study, we employed chemical proteomics to survey potential molecular targets of endoperoxides by evaluating P. falciparum proteins capable to associate with endoperoxide structure (N-346, a carboxyamino derivative of N-89). We also analyzed the protein expression profiles of malaria parasites treated with N-89 or N-251 to explore possible changes associated with the drug action. From these experiments, we found that P. falciparum endoplasmic reticulum-resident calcium binding protein (PfERC) had high affinity to the endoperoxide structure (N-346) and was decreased by treatment with N-89 or N-251. PfERC is a member of CREC protein family, a potential disease marker and also a potential target for therapeutic intervention. We propose that the PfERC is a strong candidate of the endoperoxide antimalarial's target.

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  • Andirolides H-P from the flower of andiroba (Carapa guianensis, Meliaceae) 査読

    Yuji Tanaka, Asami Sakamoto, Takanobu Inoue, Takeshi Yamada, Takashi Kikuchi, Tetsuya Kajimoto, Osamu Muraoka, Akira Sato, Yusuke Wataya, Hye Sook Kim, Reiko Tanaka

    Tetrahedron   68 ( 18 )   3669 - 3677   2012年5月

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    Three new gedunins, an andirobin, three mexicanolides, and two phragmalin-type limonoids named andirolides H (1), I (2), J (3), K (4), L (5), M (6), N (7), O (8), and P (9) were isolated from an oil of the flower of Carapa guianensis Aublet (Meliaceae). Their structures including the absolute configurations were determined by means of the NMR and CD spectra as well as FABMS. Andirolide H (1) showed antimalarial activity against Plasmodium falciparum in vitro. © 2011 Elsevier Ltd. All rights reserved.

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  • Antimalarial activity of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) and its carboxylic acid derivatives 査読

    Akira Sato, Satoru Kawai, Akiko Hiramoto, Masayuki Morita, Natsuki Tanigawa, Yukari Nakase, Yuka Komichi, Masahiro Matsumoto, Osamu Hiraoka, Kazuyuki Hiramoto, Hidekazu Tokuhara, Araki Masuyama, Masatomo Nojima, Kazutaka Higaki, Hikoya Hayatsu, Yusuke Wataya, Hye-Sook Kim

    PARASITOLOGY INTERNATIONAL   60 ( 4 )   488 - 492   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Malaria is one of the world's deadliest diseases and is becoming an increasingly serious problem as malaria parasites develop resistance to most of the antimalarial drugs used today. We previously reported the in vitro and in vivo antimalarial potencies of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) and 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-l-ol (N-251) against Plasmodium falciparum and Plasmodium berghei parasites. To improve water-solubility for synthetic peroxides, a variety of cyclic peroxides having carboxyl functionality was prepared based on the antimalarial candidate, N-251, and their antimalarial activities were determined. The reactions of N-89 and its derivatives with Fe(II) demonstrated a highly efficient formation of the corresponding carbon radical which may be suspected as a key for the antiparasitic activity. Published by Elsevier Ireland Ltd.

    DOI: 10.1016/j.parint.2011.08.017

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  • Schistosomicidal and antifecuridity effects of oral treatment of synthetic endoperoxide N-89 査読

    Toshie Taniguchi, Takashi Kumagai, Rieko Shimogawara, Shizuko Ichinose, Akiko Hiramoto, Akira Sato, Masayuki Morita, Masatomo Nojima, Hye-Sook Kim, Yusuke Wataya, Nobuo Ohta

    PARASITOLOGY INTERNATIONAL   60 ( 3 )   231 - 236   2011年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    1,2,6,7-Tetraoxaspiro[7.11]nonadecane (N-89) is a chemically synthesized compound with good efficacy against malaria parasites. We observed strong anti-schistosomal activities of N-89 both in vitro and in vivo. In a murine model with experimental infection of Schistosoma mansoni, orally administered N-89 at the dose of 300 mg/kg resulted in a significant reduction in worm burden (63%) when mice were treated at 2-weeks postinfection. Strong larvicidal effects of N-89 were confirmed in vitro; schistosomula of S. mansoni were killed by N-89 at an EC50 of 16 nM. In contrast, no significant reduction in worm burden was observed when N-89 was administered at 5 weeks postinfection in vivo. However, egg production was markedly suppressed by N-89 treatment at that time point. On microscopic observation, the intestine of N-89-treated female worms seemed to be empty compared with the control group, and the mean body length was significantly shorter than that of controls. Nutritional impairment in the parasite due to N-89 treatment was possible, and therefore quantification of hemozoin was compared between parasites with or without N-89 treatment. We found that the hemozoin content was significantly reduced in N-89 treated parasites compared with controls (P<0.001). The surface of adult worms was observed by scanning and transmission electron microscopy, but there were no apparent changes. Taken together, these observations suggested that N-89 has strong antischistosomal effects, probably through a unique mode of drug efficacy. As N-89 is less toxic to mammalian host animals, it is a possible drug candidate against schistosomiasis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

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  • Antimalarial activity of endoperoxide compound 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol 査読

    Akira Sato, Akiko Hiramoto, Masayuki Morita, Masahiro Matsumoto, Yuka Komich, Yukari Nakase, Natsuki Tanigawa, Osamu Hiraoka, Kazuyuki Hiramoto, Hikoya Hayatsu, Kazutaka Higaki, Satoru Kawai, Araki Masuyama, Masatomo Nojima, Yusuke Wataya, Hye-Sook Kim

    PARASITOLOGY INTERNATIONAL   60 ( 3 )   270 - 273   2011年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Plasmodium falciparum, the major causative parasite for the disease, has acquired resistance to most of the antimalarial drugs used today, presenting an immediate need for new antimalarial drugs. Here, we report the in vitro and in vivo antimalarial activities of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against P. falciparum and Plasmodium berghei parasites. The N-251 showed high antimalarial potencies both in the in vitro and the in vivo tests (EC(50) 2.3 X 10(-8) M; ED(50) 15 mg/kg (per oral)). The potencies were similar to that of artemisinin in vitro and greater than artemisinin's activity in vivo (p.o.). In addition, N-251 has little toxicity: a single oral administration at 2000 mg/kg to a rat gave no health problems to it. Administration of N-251 to mice bearing 1% of parasitemia (per oral 68 mg/kg, 3 times a day for 3 consecutive days) resulted in a dramatic decrease in the parasitemia: all the 5 mice given N-251 were cured without any recurrence, with no diarrhea or weight loss occurring in the 60 days of experiment. N-251 deserves more extensive clinical evaluation, desirably including future trials in the human. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

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  • Association of RNase L with a Ras GTPase-activating-like protein IQGAP1 in mediating the apoptosis of a human cancer cell-line

    Akira Sato, Tomoharu Naito, Akiko Hiramoto, Kazato Goda, Takuya Omi, Yukio Kitade, Takuma Sasaki, Akira Matsuda, Masakazu Fukushima, Yusuke Wataya, Hye Sook Kim

    FEBS Journal   277   4464 - 4473   2010年11月

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    Mammalian intracellular ribonuclease L (RNase L) is a latent endoribonuclease that functions against viral infections as an apoptosis-inducing protein, and its activity requires intracellular 5′-end-triphosphorylated-2′,5′ oligoadenylates (2-5A) as an activator. Previously, we showed that RNase L can be activated in human cancer cell line HT1080 by an RNA polymerase I inhibitor, 1-(3-C-ethynyl-β-D-ribo- pentofuranosyl)cytosine (3′-ethynylcytidine; ECyd). In ECyd-treated cells, knockdown of the RNase L resulted in a marked decrease in c-jun N-terminal kinase (JNK) phosphorylation, thereby inhibiting apoptosis. We investigate RNase L binding partners by focused proteomic approach using immunoprecipitation with anti-RNase L IgG and mass spectrometry. We found that the IQ motif-containing Ras GTPase-activating-like protein 1 (IQGAP1) can associate with RNase L, and that phosphorylation occurs on the IQGAP1. ECyd-induced JNK phosphorylation and apoptosis were inhibited when IQGAP1 was knocked down with a small interfering RNA. These results raise the interesting possibility that the RNase L-IQGAP1 association may regulate JNK phosphorylation in RNase L-madiated apoptosis. It is likely IQGAP1 works as a regulator in apoptosis.© 2010 The Authors Journal compilation © 2010 FEBS.

    DOI: 10.1111/j.1742-4658.2010.07833.x

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  • GERANYL DERIVATIVES OF ISOQUINOLINE ALKALOIDS SHOW INCREASED BIOLOGICAL ACTIVITIES 査読

    Yumi Nishiyama, Kinuko Iwasa, Suguru Okada, Sousuke Takeuchi, Masataka Moriyasu, Miyoko Kamigauchi, Junko Koyama, Atsuko Takeuchi, Harukuni Tokuda, Hye-Sook Kim, Yusuke Wataya, Kazuyoshi Takeda, Yi-Nan Liu, Pei-Chi Wu, Kenneth F. Bastow, Toshiyuki Akiyama, Kuo-Hsiung Lee

    HETEROCYCLES   81 ( 5 )   1193 - 1229   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Three types of isoquinoline alkaloids were tested for antimicrobial, cytotoxic, anti-malarial, anti-oxidant, and anti-HIV activities, as well as inhibitory activity against Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. N- or O-Geranylation contributed to increased potency in four types of activities except anti-HIV and anti-oxidant. Some types of alkaloids may be useful as lead compounds for developing potential chemotherapeutic agents. N,N-Geranylated salsolinol was significantly active in three different assays, antimicrobial, cytotoxic, and EBV-EA, and may be a most useful compound.

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  • Protein Expression Profiles of Necrosis and Apoptosis Induced by 5-Fluoro-2 '-deoxyuridine in Mouse Cancer Cells 査読

    Akira Sato, Akito Satake, Akiko Hiramoto, Yusuke Wataya, Hye-Sook Kim

    JOURNAL OF PROTEOME RESEARCH   9 ( 5 )   2329 - 2338   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    We have investigated the molecular mechanisms regulating the necrosis and apoptosis that occur on treatment of mouse mammary tumor FM3A cells with 5-fluoro-2'-deoxyuridine (FUdR), a potent anticancer agent, using the original clone F28-7 and its variant F28-7-A cells. Previously, we reported an interesting observation that FUdR induces a necrotic morphology in F28-7 but an apoptotic morphology in F28-7-A cells. We have now analyzed the protein expression profiles of these FUdR-induced necrosis and apoptosis. Thus, proteome analysis of these clones by two-dimensional gel electrophoresis and mass spectrometry showed that the cytoplasmic intermediate filament protein, cytokeratin-19, is expressed at a significantly higher level in F28-7 than in F28-7-A cells. This strong expression was detected both in untreated and FUdR-treated stages of F28-7 cells. We interpreted this phenomenon as suggesting that cytokeratin-19 possesses a function in leading the cell to apoptosis. We performed a knockdown of cytokeratin-19 expression in F28-7 cells by use of the small interfering RNA technique. Indeed, a lowering of the cytokeratin-19 expression down to the level in F28-7-A occurred, and the FUdR-induced death morphology of this knockdown F28-7 was apoptosis, instead of the necrosis usually observable in the FUdR-treated F28-7. It is known that the cytoskeletal protein cytokeratin-19 undergoes caspase-mediated degradation during apoptosis. Our present finding provides an interesting possibility that cytokeratin-19 may have a key role in regulating cell-death morphology.

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  • Selective accumulation of rhodacyanine in plasmodial mitochondria is related to the growth inhibition of malaria parasites 査読

    Morisaki D, Kim H.-S, Inoue H, Terauchi H, Kuge S, Naganuma A, Wataya Y, Tokuyama H, Ihara M, Takasu K

    Chemical Science   1 ( 2 )   206 - 209   2010年

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  • Antimalarial artemisinin and tetraoxane endoperoxides behave differently in the oxidative degradation of unsaturated phospholipid

    Naokazu Kumura, Hirotaka Furukawa, Arnold N. Onyango, Minoru Izumi, Shuhei Nakajima, Hideyuki Ito, Tsutomu Hatano, Hye-Sook Kim, Yusuke Wataya, Naomichi Baba

    CHEMISTRY AND PHYSICS OF LIPIDS   160   S28 - S29   2009年8月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

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  • Role of RNase L in apoptosis induced by 1-(3-C-ethynyl-β-d-ribo- pentofuranosyl)cytosine

    Tomoharu Naito, Tatsushi Yokogawa, Satoshi Takatori, Kazato Goda, Akiko Hiramoto, Akira Sato, Yukio Kitade, Takuma Sasaki, Akira Matsuda, Masakazu Fukushima, Yusuke Wataya, Hye Sook Kim

    Cancer Chemotherapy and Pharmacology   63   837 - 850   2009年4月

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    Purpose: 1-(3-C-Ethynyl-β-d-ribo-pentofuranosyl)cytosine (ECyd), a ribonucleoside analog, has a potent cytotoxic activity against cancer cells. The present studies have been performed to elucidate the overall mechanisms of ECyd-induced apoptotic cell death. Methods: Cultured cells of mouse mammary carcinoma FM3A and human fibrosarcoma HT 1080 lines were used. The efficacy of RNA synthesis inhibition by ECyd was assessed by kinetic analysis using nuclei isolated from FM3A cells. RNA status in ECyd-treated cells was investigated by Northern blots, and the cleavage sites of RNA were identified by rapid amplification of 5′ cDNA ends (5′-RACE). The effect of protein functions on the ECyd-induced apoptotic pathway was analyzed by siRNA and immunohistochemical techniques. Apoptotic cells were detected by TdT-mediated dUTP-biotin Nick End Labeling (TUNEL) assay. Results: ECyd induces inhibition of RNA synthesis in vitro and in vivo, which appears to be a major cause for the apoptosis. It is known that ECyd is converted inside the cell into its 5′-triphosphate (ECTP). We have now found in test-tube experiments that ECTP strongly inhibits the activity of RNA polymerase I by competing with CTP. In the absence of robust RNA synthesis, the cellular RNAs would be destined to break down. RNase L was found to be playing a role in the breakdown: thus, the 28S rRNA-fragmentation pattern observed for the ECyd-treated cells was very similar to that observable in an in vitro treatment of the 28S ribosomes with RNase L. Association of RNase L with the cytotoxic action of ECyd was confirmed by use of the siRNA-mediated suppression of the cellular RNase L. Thus, the cells in which the RNase L was knocked-down were highly resistant to the cytotoxic action of ECyd. Further events, downstream of the RNase L action that can lead to the eventual apoptosis, would conceivably involve the phosphorylation of c-jun N-terminal kinase and subsequent decrease in mitochondrial membrane-potential. Evidence to support this flow of events was obtained by siRNA-experiments. Conclusion: The results from this study demonstrated that RNase L is activated after the inhibition of RNA polymerase, and induces mitochondria-dependent apoptotic pathway. We propose this new role for RNase L in the apoptotic mechanism. These findings may open up the possibility of finding new targets for anticancer agents. © 2008 Springer-Verlag.

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  • Toxoplasma gondii: A simple high-throughput assay for drug screening in vitro 査読

    ChunMei Jin, Kusuma Kaewintajuk, JingHua Jiang, WooJin Jeong, Masaki Kamata, Hye-Sook Kim, Yusuke Wataya, Hyun Park

    EXPERIMENTAL PARASITOLOGY   121 ( 2 )   132 - 136   2009年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Toxoplasma gondii is the etiologic agent of toxoplasmosis. Although the combination of sulfadiazine and pyrimethamine is used as therapy for this disease, these drugs can have serious side effects and its use is limited in pregnancy. Therefore there is a need for new anti-T gondii drugs in the clinic. Some systems for T. gondii drug screening have been described, but these have limitations and can be difficult. In order to solve these problems, we established a system to screen drugs in vitro that involved using cell viability methods to calculate drug selectivities, which are Trypan blue, [3-(4,5-dimethylthiazol-zyl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazoliuzolium, inner salt] (MTS) method and lactate dehydrogenase (LDH) assay. These assays were simple to establish and perform. The IC(50) values calculated from the morphological assay were not significantly different from the EC(50) values calculated using the other three methods. In particular, the results of the morphological assay showed a distinct association with the MTS assay (R = 0.9841). These assays could be used for a wide range of applications in the screening of new drugs and may provide an alternative to the techniques currently used to screen for candidate anti-T. gondii compounds in vitro. In this study, we also tested many compounds and identified some that had a good anti-T gondii effect in vitro based on the MTS assay. This simple and fast system allowed us to determine which compounds to investigate further using in vivo experiments. (C) 2008 Elsevier Inc. All rights reserved.

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  • Synthesis of Novel Conjugates of Tetraoxane Endoperoxide with Bis(Quaternary Ammonium Salts)

    Naokazu Kumura, Hirotaka Furukawa, Michiyo Kobayashi, Arnold N. Onyango, Minoru Izumi, Shuhei Nakajima, Hye-Sook Kim, Yusuke Wataya, Naomichi Baba

    Biosci. Biotechnol. Biochem.   73 ( 1 )   217 - 220   2009年

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  • Different behavior of artemisinin and tetraoxane in the oxidative degradation of phospholipid

    Kumura, N, Furukawa, H, Onyango, A.N, Izumi, M, Nakajima, S, Ito, H, Hatano, T, Kim, H.-S, Wataya, Y, Baba, N

    Chemistry and Physics of Lipids   160 ( 2 )   114 - 120   2009年

  • Synthesis and silencing properties of siRNAs possessing lipophilic groups at their 3 '-termini

    Yoshihito Ueno, Koshi Kawada, Tomoharu Naito, Aya Shibata, Kayo Yoshikawa, Hye-Sook Kim, Yusuke Wataya, Yukio Kitade

    BIOORGANIC & MEDICINAL CHEMISTRY   16 ( 16 )   7698 - 7704   2008年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Short-interfering RNAs (siRNAs) conjugated with lipophilic groups at their 3'-termini were synthesized. The properties of the synthesized siRNAs were examined in detail, and it was found that at low concentrations, their silencing abilities were dependent on the positions of the modi. cations and the types of organic molecules attached. Although the modi. cation of siRNAs with palmitic acid or oleic acid at the 3'-end slightly reduced their silencing activities, siRNAs had enough abilities to induce RNAi at 10 nM concentrations. On the other hand, the modi. cation of siRNAs with cholesterol at the 3'-end of the passenger strand was tolerated; however, the modi. cation at the guide strand significantly reduces its silencing activity. The siRNAs modified with the lipophilic groups did not possess ability to penetrate the plasma membranes of HT-1080 cells without the transfection reagent. However, the results described in this report will aid in designing novel siRNAs with cell membrane-permeable molecules. (C) 2008 Elsevier Ltd. All rights reserved.

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  • Gene expression profiles of necrosis and apoptosis induced by 5-Fluoro-2ユ-deoxyuridine..

    Sato, A, Hiramoto, A, Uchikubo, Y, Miyazaki, E, Satake, A, Naito, T, Hiraoka, O, Miyake, T, Kim, H.-S, Wataya, Y

    Genomics,   92 ( 1 )   9 - 17   2008年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Detection of malaria parasites in mosquitoes from the malaria-endemic area of Chakaria, Bangladesh

    Akter Tangin, Yuka Komichi, Yukiko Wagatsuma, Haque Rashidul, Yusuke Wataya, Hye-Sook Kim

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   31 ( 4 )   703 - 708   2008年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Malaria is one of the major public health problems of Bangladesh. We investigated the mosquito populations infected with malaria parasites in a malaria-endemic area Chakaria, Bangladesh, where Anopheles dirus and Anopheles minimus are the principal vectors. Anopheles mosquitoes were collected with a CDC miniature light trap from inside households in June 2007. A total of 868 mosquitoes were collected, among which females numbered 669 (77.1%). The species of female Anopheles mosquitoes were identified morphologically, and 651 were A. minimus and the remaining 18 were other Anopheles species. Malaria parasite DNA from individual female mosquitoes was extracted and distinguished using the microtiter plate hybridization (MPH) technique targeting the 18S rRNA of human malaria parasites. Nineteen mosquitoes were malaria parasite positive: 12 for Plasmodium falciparum, 1 for Plasmodium vivax, and 6 for both R falciparum and P vivax. This is the first time that the MPH technique was used for distinguishing malaria parasites in mosquitoes and the first report from Chakaria. Our results may contribute to planning and assessing malaria control strategies in Chakaria.

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  • Association of nuclear membrane protein lamin B1 with necrosis and apoptosis in cell death induced by 5-fluoro-2 '-deoxyuridine

    Akira Sato, Akiko Hiramoto, Akito Satake, Eriko Miyazaki, Tomoharu Naito, Yusuke Wataya, Hye-Sook Kim

    NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS   27 ( 5 )   433 - 438   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS INC  

    We report that anticancer 5-fluoro-2'-deoxyuridine (FUdR) shows cytotoxicity against mouse cancer cell line FM3A, using a progeny clone F28-7 and its variant F28-7-A. In this process, the cell-death morphology is different between F28-7 and F28-7-A cells, that is, necrosis in F28-7 but apoptosis in F28-7-A cells. In the proteomic analysis of these cells before their exposure to FUdR, the nuclear inner-membrane protein lamin B1 is up-regulated in F28-7 but not in F28-7-A, suggesting that lamin B1 may possess a function to regulate the morphology of cell-death. A knockdown of lamin B1 expression in F28-7 cells was performed by use of the small interfering RNA technique, resulting in a decrease of the lamin B1-expression level down to the level in F28-7-A. Remarkably, the FUdR-induced death morphology of this knocked-down F28-7 was apoptosis, definitely different from the necrosis that occurs in the FUdR-treated original F28-7. Thus, the swelling feature for the necrosis was no longer observable, and instead cell shrinkage typical of apoptosis took place in almost all the cells examined. This finding suggests a new role for lamin B1 as a regulator in cell death.

    DOI: 10.1080/15257770802086864

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  • In vitro antimalarial activity of flavonoids and chalcones

    Soon Sung Lim, Hye-Sook Kim, Dong-Ung Lee

    BULLETIN OF THE KOREAN CHEMICAL SOCIETY   28 ( 12 )   2495 - 2497   2007年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KOREAN CHEMICAL SOC  

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  • Preparation of quinoline hexose analogs as novel chloroquine-resistant malaria treatments (1). Synthesis of 4-hydroxyquinoline-beta-glucosides

    Hiroshi Suzuki, Nagwa S. M. Aly, Yusuke Wataya, Hye-Sook Kim, Ikumi Tamai, Masaki Kita, Daisuke Uemura

    CHEMICAL & PHARMACEUTICAL BULLETIN   55 ( 5 )   821 - 824   2007年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Quinoline hexose analogs are expected to be useful as novel agents for treatment of chloroquine-resistant malaria. Here, we report preparation of 4-hydroxy quinoline-beta-glucosides from anilines in 4 steps.

    DOI: 10.1248/cpb.55.821

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  • Proteome analysis of new antimalarial endoperoxide against Plasmodium falciparum

    Nagwa S. M. Aly, Akiko Hiramoto, Hitomi Sanai, Osamu Hiraoka, Kazuyuki Hiramoto, Hiroyuki Kataoka, Jin-Ming Wu, Araki Masuyama, Masatomo Nojima, Satoru Kawai, Hye-Sook Kim, Yusuke Wataya

    PARASITOLOGY RESEARCH   100 ( 5 )   1119 - 1124   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    N-89, a new antimalarial endoperoxide, was selected as a promising antimalarial compound showing high activity and selectivity. To study the mechanism of N-89 action, N-89 resistant strain (NRC10) was obtained by intermittent drug pressure. NRC10 bad a tenfold increase in the EC50 value of N-89. No cross-resistance was obtained with other antimalarial compounds. Comparative proteome analysis of N-89 sensitive and NRC10 strains revealed over-expression of 12 spots and down-regulation of 14 spots in NRC10. Fifteen proteins were identified of Plasmodium falciparum origin. The identified proteins representing several functions, mainly related to the glycolytic pathway, and metabolism of protein and lipid. Our results suggest that identified proteins may be candidates of antimalarial endoperoxide targets.

    DOI: 10.1007/s00436-007-0460-8

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  • Design, synthesis and in vitro antimalarial activity of spiroperoxides

    Hong-Xia Jin, Qi Zhang, Hye-Sook Kim, Yusuke Wataya, He-Hua Liu, Yikang Wu

    TETRAHEDRON   62 ( 33 )   7699 - 7711   2006年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Several spiroperoxy antimalarial compounds were designed and synthesized using the hydrogen peroxide in UHP (urea-H2O2 complex) as the source of the peroxy bond. Incorporation of the H2O2 into the organic molecule framework through ketal exchange reaction in the present cases was greatly facilitated by the potential to form a five- or six-membered cyclic hemiketal due to the presence of a hydroxyl group gamma or beta to the ketone carbonyl group. When the electron-withdrawing group in the Michael acceptor was a nitro group, the closure of the peroxy ring occurred readily under the hydroxidation conditions. Presence of a benzene ring fused to the peroxy ling effectively reduced the degrees of freedom in the transition state for the ring-closure step and made the otherwise very difficult seven-membered 1,2-dioxepane rather easy to form through the intramolecular Michael addition. (c) 2006 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tet.2006.05.065

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  • Antimalarial effect of bis-pyridinium salts, N,N '-hexamethylenebis(4-carbamoyl-1-alkylpyridinium bromide)

    K Fujimoto, D Morisaki, M Yoshida, T Namba, K Hye-Sook, Y Wataya, H Kourai, H Kakuta, K Sasaki

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   16 ( 10 )   2758 - 2760   2006年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The in vitro antimalarial activity of bis-pyridinium salts, N,N'-hexamethylenebis(4-carbamoyl-1-decylpyridinium bromide) and their derivatives, against the Plasmodium falciparum FCR-3 strain (ATCC 30932, chloroquine-sensitive) was evaluated. All test compounds exhibited antimalarial activity over a concentration range of 3.5 mu M to 10 nM. The chain length of the N1-alkyl moiety was found to be very beneficial in terms of antimalarial activity, and in this series of compounds, the most appropriate N1-alkyl chain length was found to be eight. (C) 2006 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmcl.2006.02.030

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  • Trichomonicidal Activity of Herbal Extracts Used in Traditional Medicine in Korea.

    Youn-Chul Kim, Jae-Sook Ryu, Hyoung-Jun Kim, Kyung-Min Choi, Hye-Sook Kim, Hyun Park

    Korean J.Oriental Physiology & Pathology   2006年

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  • A case of mixed infection of Plasmodium falciparum and Plasmodium ovale from nigeria: Difficulty of microscopic diagnosis after inappropriate treatment.

    Haruki, K, Kaku, K, Yamamoto, T, Katagiri, T, Sakurai, Y, Hirose, W, Kim, H.-S, Wataya, Y

    Clinic. Parsitol.,   2006年

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  • 1,2,4,5-Tetraoxacycloalkanes: Synthesis and antimalarial activity

    A Masuyama, JM Wu, M Nojima, HS Kim, Y Wataya

    MINI-REVIEWS IN MEDICINAL CHEMISTRY   5 ( 11 )   1035 - 1043   2005年11月

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    記述言語:英語   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    In this short review the methods of preparation of novel 1,2,4,5-tetraoxacycloalkanes and the related peroxides are summarized, with the emphasis on the usefulness of 1,1-bishydroperoxides as the precursor. Also, their antimalarial activities in vitro and in vivo are discussed.

    DOI: 10.2174/138955705774575255

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  • Synthesis and biological activity of fatty acid derivatives of quinine

    N Kumura, M Izumi, S Nakajima, S Shimizu, HS Kim, Y Wataya, N Baba

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   69 ( 11 )   2250 - 2253   2005年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    Derivatives of quinine with fatty acids including polyunsaturated fatty acids were prepared. They showed moderate antimalarial activity as compared with quinine itself using Plasmodium falciparum. The activities were not dependent on whether the fatty acyl group was saturated or unsaturated. On the other hand, the derivatives showed significantly higher cytotoxicity against a mammary tumor cell line FM3A than quinine itself. Calculating from these data, an acetyl derivative of quinine with the shortest acyl group was found to give the highest selectivity.

    DOI: 10.1271/bbb.69.2250

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  • Synthesis and in vitro antimalarial activity of several simple analogues of peroxyplakoric acid

    HH Liu, HX Jin, Q Zhang, YK Wu, HS Kim, Y Wataya

    CHINESE JOURNAL OF CHEMISTRY   23 ( 11 )   1469 - 1473   2005年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-V C H VERLAG GMBH  

    Several simple analogues of peroxyplakoric acid were synthesized by using Kobayashi's method to construct the key 1,2-dioxane core and tested in vitro for antimalarial activity. The scope and limitation of the method was also briefly examined.

    DOI: 10.1002/cjoc.200591469

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  • Co-catalyzed autoxidation of alkene in the presence of silane. The effect of the structure of silanes on the efficiency of the reaction and on the product distribution

    JM Wu, S Kunikawa, T Tokuyasu, A Masuyama, M Nojima, HS Kim, Y Wataya

    TETRAHEDRON   61 ( 42 )   9961 - 9968   2005年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    A systematic investigation of the structural effect of silanes on the Co-catalyzed reductive oxygenation of alkene in the presence of silane (Mukaiyama-Isayama reaction) showed that the efficiency of the reaction decreases with the increase of the steric bulk of the silanes. A similar trend was observed for the metal-exchange reaction between Co(III)-alkylperoxo complex and silane, too. The peroxidation of (S)-limonene, followed by deprotection of the derived silyl peroxides, provides a mixture of the corresponding monocyclic hydroperoxide 24 and the bicyclic one 25, the ratio being a marked function of the steric bulk of silanes. (c) 2005 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tet.2005.08.025

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  • Gastrodia elata blume and an active component, p-hydroxybenzyl alcohol reduce focal ischemic brain injury through antioxidant related gene expressions

    SJ Yu, Kim, JR, CK Lee, JE Han, JH Lee, HS Kim, JH Hong, SG Kang

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   28 ( 6 )   1016 - 1020   2005年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Ischaemic stroke is a leading cause of death and long-lasting disability. Gastrodia elata blume (GEB) is a Chinese herb that is widely used to treat convulsive disorders, such as epilepsy, and p-hydroxybenzyl alcohol (HBA) is the active ingredient in GEB. The present study was conducted to evaluate the effects of GEB and HBA on the brain damage and transcriptional levels of Protein disulfide isomerase (PDI) and 1-Cys peroxiredoxin (1-Cys Prx) genes known to play a role in antioxidant systems after transient focal ischemia in the rat brain. Focal ischemia was induced in rats by middle cerebral artery occlusion (MCAO). All animals underwent ischemia for I h, followed by 24 h of reperfusion. Coronal brain slices were stained with 2,3,5-triphenyltetrazolium chloride or total RNA was extracted for the analysis of gene expression. Histopathologic analysis revealed a significant (p < 0.05) decrease in infarct size in the ipsilateral brain with GEB extracts or HBA. Moreover, the levels of PDI and 1-Cys Prx transcription were significantly increased in the GEB extract- or HBA-treated group compared with the untreated group (p < 0.05). This study therefore indicated that GEB and HBA provide neuroprotection by preventing brain damage through the increased expression of genes encoding antioxidant proteins after transient focal cerebral ischemia and may be effective as neuroprotective agents at the cellular and molecular levels in the brain.

    DOI: 10.1248/bpb.28.1016

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  • Synthesis and evaluation of -carbolinium cations as new antimalarial agents based on pi-delocalized lipophilic cation (DLC) hypothesis.

    Takasu, K, Shimogama, T, Saiin, C, Kim, H.-S, Wataya, Y, Brun, R, Ihara, M

    Chem. Pharm. Bull.,   53 ( 6 )   653 - 661   2005年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1248/cpb.53.653

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  • Synthesis of novel siRNAs having thymidine dimers consisting of a carbamate or a urea linkage at their 3 ' overhang regions and their ability to suppress human RNase L protein expression

    Y Ueno, T Naito, K Kawada, A Shibata, HS Kim, Y Wataya, Y Kitade

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   330 ( 4 )   1168 - 1175   2005年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    In order to examine the effect of modifications at the 3' overhang regions of short interfering RNAs (siRNAs) oil their gene-silencing activities, we designed and synthesized novel siRNAs having thymidine dimers consisting of a carbamate or a urea linkage at their 3' overhang regions. Suppression of human RNase L protein expression by these siRNAs was analyzed by immunoblot with RNase L-specific antibody. It was found that, at 24 h post-transfection, the modified siRNAs having the thymidine dimers with the carbamate and urea linkage suppress the protein expression 78 and 37 times more efficiently than that with the natural phosphodiester linkage, respectively. Furthermore, the siRNA containing the carbamate linkage was 37 times more resistant to nucleolytic degradation by snake venom phosphodiesterase than the siRNA consisting of the natural phosphodiester linkage. Thus, the RNA duplexes having the thymidine dimers with the carbamate or urea linkage at their 3' overhang regions will be promising candidates for novel siRNA molecules to down-regulate protein expression. (c) 2005 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2005.03.100

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  • Synthesis of 5’-methylenearisteromycin and its 2-fluoro congener with potent antimalarial activity due to the parasite S-adenosyl homocysteine hydrolase Inhibition.

    Takagi,T, Sukeda,M, Kim,H.-S, Wataya,Y, Kitade,Y, Matsuda,A, Shuto. S

    Org. Biomol. Chem.,   3 ( 7 )   1245 - 1251   2005年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1039/b418829b

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  • Inhibitory mechanisms of 1-(3-C-ethynyl-beta-D-RIBO-pentofuranosyl)uracil (EUrd) on RNA synthesis

    T Yokogawa, T Naito, H Kanda, S Takatori, K Takenaka, T Sasaki, A Matsuda, M Fukushima, HS Kim, Y Wataya

    NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS   24 ( 3 )   227 - 232   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS INC  

    1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)uracil (EUrd) is an antimetabolite that strongly inhibits RNA synthesis and shows a broad antitumor activity in vitro and in vivo. In mouse mammary tumor FM3A cells, EUrd is sequentially phosphorylated to its 5-triphosphate, EUTP, a major metabolite, and the RNA synthesis is inhibited proportionally to its intracellular accumulation. To study the inhibitory mechanisms of EUrd on RNA synthesis, we have performed the kinetic analysis of EUTP on RNA polymerization using isolated nuclei. RNA synthesis was inhibited competitively by EUTP. The inhibition constant, K-i was much lower than the K-m value of UTP (K-i value of EUTP, 84 nM; K-m value of UTP, 13 μ M), indicating that the high affinity of EUTP could contribute to the specific inhibition of RNA synthesis. As a result of RNA synthesis inhibition, EUrd, but not ara-C, induced shrinkage of nucleoli, which are the main sites for RNA synthesis in FM3A cells. Thus, the strong affinity of E UTP to RNA polymerase and specific inhibition of RNA synthesis could contribute to its antitumor effect. EUrd is expected to be a new antitumor drug, possessing a strong inhibitory effect on the synthesis of RNA.

    DOI: 10.1081/NCN-200055727

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  • Sequence analysis of the 5´-flanking regions of human dihydropyrimidine dehydrogenase gene: Identification of a new polymorphism related with effects of 5-fluorouracil.

    Hasegawa,T, Kim,H.-S, Fukushima,M, Wataya,Y

    Nucleosides Nucleotides Nucleic Acids,   24 ( 4 )   233 - 242   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1081/NCN-200059676

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  • Duffy antigen is important for the lethal effect of the lethal strain of Plasmodium yoelii 17XL. 査読 国際誌

    Akimitsu N, Kim HS, Hamamoto H, Kamura K, Fukuma N, Arimitsu N, Ono K, Wataya Y, Torii M, Sekimizu K

    Parasitology research   93 ( 6 )   499 - 503   2004年8月

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  • π-Delocalized β-carbolinium cations as potential antimalarials 査読

    Takasu K, Shimogama T, Saiin C, Kim H.-S, Wataya Y, Ihara M

    Bioorganic and Medicinal Chemistry Letters   14 ( 7 )   1689 - 1692   2004年

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  • Antimalarial activity of herbal extracts used in traditional medicine in Korea

    H Park, MS Kim, BH Jeon, TK Kim, YM Kim, J Ahnn, DY Kwon, Y Takaya, Y Wataya, HS Kim

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   26 ( 11 )   1623 - 1624   2003年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Aqueous extracts of 6 traditional Korean medicines used to treat malaria were tested in vitro for their antimalarial activity against Plasm odium falciparum. The EC50 values for the herbal extracts were in the range 1.4-8.1 mug/ml. Significant antimalarial activity was observed with Coptis japonica (EC50 = 1.4 mug/ml), but it demonstrated no selective toxicity (selectivity = 1). In contrast, Kalopyanax pictus showed antimalarial activity (EC50 = 4.6 mug/ml) and higher selective toxicity (>4). This indicated that K. pictus may be potent for a new antimalarial agent.

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  • Synthesis of 2-fluoronoraristeromycin and its inhibitory activity against Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase

    Y Kitade, H Kojima, F Zulfiqur, HS Kim, Y Wataya

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   13 ( 22 )   3963 - 3965   2003年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Palladium-coupling reaction of (IS, 4 R)-cis-4-acetoxy-2-cyclopenten-1-ol with sodium salt of 2-fluoroadenine resulted in the formation of (IS,4R)-4-(6-amino-2-fluoro-9H-purin-9-yl)cyclopent-2-en-1-ol. Subsequent oxidation was carried out with osmium tetraoxide (OsO4) in the presence of 4-methylmorpholine N-oxide (NMO) to give 2-fluoronoraristeromycin, possessing significant inhibitory activity against recombinant Plasm odium falciparum SAH hydrolase. (C) 2003 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmcl.2003.08.074

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  • Unique properties of respiratory chain in Plasmodium falciparum mitochondria

    Fumika Mi-Ichi, Satoru Takeo, Eizo Takashima, Tamaki Kobayashi, Hye Sook Kim, Yusuke Wataya, Akira Matsuda, Motomi Torii, Takafumi Tsuboi, Kiyoshi Kita

    Advances in Experimental Medicine and Biology   531   117 - 133   2003年9月

  • Synthesis of antimalarial yingzhaosu a analogues by the peroxidation of dienes with Co(II)/O-2/Et3SiH

    T Tokuyasu, S Kunikawa, M Abe, A Masuyama, M Nojima, HS Kim, K Begum, Y Wataya

    JOURNAL OF ORGANIC CHEMISTRY   68 ( 19 )   7361 - 7367   2003年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Co(II)-catalyzed peroxidation of dienes including (S)-limonene in the presence of molecular oxygen and triethylsilane provided in each case the corresponding 2,3-dioxabicyclo[3.3.1] nonane derivatives via the intramolecular cyclization of the unsaturated peroxy radical intermediates. The product composition was remarkably influenced by the structure of the dienes, the nature of the solvents, and the concentration of the substrates and the catalyst. Some of the yingzhaosu A analogues obtained in this study showed notable antimalarial activities in vitro.

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  • Metabolites of febrifugine and its synthetic analogue by mouse liver S9 and their antimalarial activity against Plasmodium malaria parasite

    S Hirai, H Kikuchi, HS Kim, K Begum, Y Wataya, H Tasaka, Y Miyazawa, K Yamamoto, Y Oshima

    JOURNAL OF MEDICINAL CHEMISTRY   46 ( 20 )   4351 - 4359   2003年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Quinazolinone type alkaloids, febrifugine (1) and isofebrifugine (2), isolated from Dichroa febrifuga roots, show powerful antimalarial activity against Plasmodium falciparum. Unfortunately, their emetic effect and other undesirable side effects have precluded their clinical use for malaria. Because of their antimalarial potency, analogues were searched for, with the goal of preserving the strong antimalarial activity, while dramatically reducing side effects. We expected that compounds useful in drug development would exist in metabolites derived from I and Df-1 (3), the condensation product of 1 with acetone, by mouse liver S9. Feb-A and -B (4 and 5) were isolated as the major metabolites of 1. In addition to 4 and 5, feb-C and -D (6 and 7) were also purified from the metabolic mixture of 3. Compounds 4 and 5 were compounds oxidized at C-6 and C-2 of the quinazolinone ring of 1, respectively. Compounds 6 and 7, derived from 3, also bear febrifugine type structures in which the 4"- and 6"-positions of the piperidine ring of 1 were oxidized. In vitro antimalarial. and cytotoxic tests using synthetically obtained racemic 4-6 and enantiomerically pure 7 demonstrated that 4 and 6 had antimalarial activity against P. falciparum, of similar potency to that of 1, with high selectivity. The antimalarial. activity of 5 and 7, however, was dramatically decreased in the test. The in vitro antimalarial activity of analogues 22 and 43, which are stereoisomers of 4 and 6, was also evaluated, showing that 22 is active. The results suggest that basicity of both the 1- and the 1"-nitrogen atoms of 1 is crucial in conferring powerful antimalarial activity. Racemic 4 and 6 exhibited powerful in vivo antimalarial activity against mouse malaria P. berghei, and especially, no serious side effects were observed with 4. Thus, the metabolite 4 appears to be a promising lead compound for the development of new types of antimalarial drugs.

    DOI: 10.1021/jjm0302086

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  • In vitro antimalarial activity of metalloporphyrins against Plasmodium falciparum

    K Begum, HS Kim, Kumar, V, Stojiljkovic, I, Y Wataya

    PARASITOLOGY RESEARCH   90 ( 3 )   221 - 224   2003年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER-VERLAG  

    The in vitro antimalarial activity against Plasmodium falciparum and heme polymerization were evaluated for ten metalloporphyrins: gallium protoporphyrin IX (GaPPIX), sodium salt of gallium protoporphyrin IX, silver protoporphyrin IX, palladium protoporphyrin IX, cobalt protoporphyrin IX, manganese protoporphyrin IX, tin protoporphyrin IX (SnPPIX), chromium protoporphyrin IX, gallium deuteroporphyrin IX (GaDPIX) and gallium hematoporphyrin IX. Metalloporphyrins inhibited parasite growth with 50% inhibitory concentrations (IC50) ranging from 15.5 muM to 190 muM. In trophozoite lysate-mediated heme polymerization assays, SnPPIX, GaPPIX and GaDPIX exerted potent inhibitory activity similar to that of artemisinin and chloroquine.

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  • In vitro antiplasmodial activity of antimalarial medicinal plants used in Vietnamese traditional medicine

    Q Le Tran, Y Tezuka, JY Ueda, NT Nguyen, Y Maruyama, K Begum, HS Kim, Y Wataya, QK Tran, S Kadota

    JOURNAL OF ETHNOPHARMACOLOGY   86 ( 2-3 )   249 - 252   2003年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Among 42 extracts, prepared from 14 medicinal plants used in Vietnamese traditional medicine to treat malaria, 24 were found to have antiplasmodial activity by inhibiting the growth of the chloroquine-resistant Plasmodium falciparum strain FCR-3 with EC50 values less than 10 mug/ml. Each medicinal plant possessed at least one active extract. The methanol extract of Coscinium fenestratum had the strongest antiplasmodial activity with EC50 value of 0.5 mug/ml. Activity-guided fractionation led to identification of berberine as the major active constituent. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0378-8741(03)00045-X

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  • Parallel synthesis of antimalarial rhodacyanine dyes by the combination of three components in one pot

    K Takasu, H Terauchi, H Inoue, HS Kim, Y Wataya, M Ihara

    JOURNAL OF COMBINATORIAL CHEMISTRY   5 ( 3 )   211 - 214   2003年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    DOI: 10.1021/cc020119z

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  • Antimalarial activity of novel 1,2,5,6-tetraoxacycloalkanes and 1,2,5-trioxacycloalkanes

    HS Kim, E Begum, N Ogura, Y Wataya, Y Nonami, T Ito, A Masuyama, M Nojima, KJ McCullough

    JOURNAL OF MEDICINAL CHEMISTRY   46 ( 10 )   1957 - 1961   2003年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Photooxygenation of 2-phenylnorbornene 1 in the presence of 30% aqueous hydrogen peroxide afforded 1,2-bishydroperoxide 3, which could be cycloalkylated on treatment with silver oxide and a 1,omega-diiodoalkane to provide the tricyclic peroxides 12. Trimethylsilylation of 3 followed by TMSOTf-catalyzed cyclocondensation with carbonyl compounds led to the formation of the tricyclic peroxides 14 containing a 1,2,4,5-tetroxepane structure. Photooxygenation of 1 in the presence of either unsaturated hydroperoxides or unsaturated alcohols followed by bis(collidine)iodine hexafluorophosphate promoted cyclization gave the corresponding cyclic peroxides 15-17. Several of these cyclic peroxides showed substantial antimalarial activity particularly in vitro.

    DOI: 10.1021/jm020387b

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  • New semisynthetic quassinoids with in vivo antimalarial activity

    N Murakami, M Sugimoto, M Kawanishi, S Tamura, HS Kim, K Begum, Y Wataya, M Kobayashi

    JOURNAL OF MEDICINAL CHEMISTRY   46 ( 4 )   638 - 641   2003年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    On the basis of a comparative analysis for stability in mouse serum between 15-O-acetylbruceolide and bruceolide 15-methyl carbonate, several 3,15-dialkyl carbonates of bruceolide were synthesized and their in vitro antimalarial activity was assessed. Methyl, ethyl, and isopropyl carbonates with pronounced in vitro activity were further evaluated for in vivo antimalarial potency. Both the methyl and ethyl carbonates significantly increased the life span of mice as compared with 3,15-di-O-accetylbruceolide and chloroquine.

    DOI: 10.1021/jm0201971

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  • Transformation of Cinchona alkaloids into 1-N-oxide derivatives by endophytic Xylaria sp isolated from Cinchona pubescens

    H Shibuya, C Kitamura, S Maehara, M Nagahata, H Winarno, P Simanjuntak, HS Kim, Y Wataya, K Ohashi

    CHEMICAL & PHARMACEUTICAL BULLETIN   51 ( 1 )   71 - 74   2003年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    The microbial transformation of four Cinchona alkaloids (quinine, quinidine, cinchonidine, and cinchonine) by endophytic fungi isolated from Cinchona pubescens was investigated. The endophytic filamentous fungus Xylaria sp. was found to transform the Cinchona alkaloids into their 1-N-oxide derivatives.

    DOI: 10.1248/cpb.51.71

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  • Acute disseminated encephalomyelitis following Plasmodium vivax malaria

    Tomohiko Koibuchi, Tetsuya Nakamura, Toshiyuki Miura, Tokiomi Endo, Hitomi Nakamura, Takashi Takahashi, Hye-Sook Kim, Yusuke Wataya, Kazushige Washizaki, Kouki Yoshikawa, Aikichi Iwamoto

    Journal of Infection and Chemotherapy   9 ( 3 )   254 - 256   2003年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Japan  

    A 24-year-old Japanese man showed neurological disturbances 2 weeks after complete recovery from Plasmodium vivax infection. Magnetic resonance (MR) images of the brain showed multiple high-intensity spotty lesions in the left cerebral cortex and subcortex. Cerebrospinal fluid examination, including polymerase chain reaction analysis for viruses, revealed no sign of active infection. Repeated blood smears were negative for malaria. We diagnosed acute disseminated encephalomyelitis (ADEM) following Plasmodium vivax malaria from the clinical course and MR images. ADEM should be regarded as one of the neurological complications after malarial infection.

    DOI: 10.1007/s10156-003-0244-8

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  • Iron(II)-promoted rearrangement of 1,4-diaryl-2,3-dioxabicyclo[2.2.2]oct-5-enes: a mechanism distinct from that postulated previously

    M Kamata, C Satoh, HS Kim, Y Wataya

    TETRAHEDRON LETTERS   43 ( 46 )   8313 - 8317   2002年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Reactions of 1,4-diaryl-2,3-dioxabicyclo[2.2.2]oct-5-enes 1a-c (la: Ar=p-FC6H4, 1b: Ar=C6H5 1c: Ar=p-MeC6H4) with FeBr2 afforded syn-1,2;3,4-bis(epoxy)-1,4-diarylcyclohcxanes 4a-c and cis-3,6-diaryl-2,3-epoxycyclohexanones 5a-c as major products instead of the previously reported 1-aroyl-3-aryl-2,3-epoxycyclopentanes 2a-c. (C) 2002 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0040-4039(02)02024-5

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  • Antimalarial activity of yingzhaosu A analogues

    HS Kim, H Begum, N Ogura, Y Wataya, T Tokuyasu, A Masuyama, M Nojima, KJ McCullough

    JOURNAL OF MEDICINAL CHEMISTRY   45 ( 21 )   4732 - 4736   2002年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Iodonium ion mediated cyclization of unsaturated hydroperoxides 1 afforded the expected yingzhaosu A analogues 2. In some cases, however, the corresponding cyclic ethers 5 were formed competitively with the cyclic peroxides 2, the ratios of these two products being a marked function of the structure of the starting materials. Some of the cyclic peroxides 2 showed significant antimalarial activities in vitro and in vivo.

    DOI: 10.1021/jm020208q

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  • Potent antimalarial febrifugine analogues against the Plasmodium malaria parasite

    H Kikuchi, H Tasaka, S Hirai, Y Takaya, Y Iwabuchi, H Ooi, S Hatakeyama, HS Kim, Y Wataya, Y Oshima

    JOURNAL OF MEDICINAL CHEMISTRY   45 ( 12 )   2563 - 2570   2002年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Although febrifugine (1) and isofebrifugine (2), alkaloids isolated from roots of the Dichroa febrifuga plant, show powerful antimalarial activity against Plasmodium falciparum, strong side effects such as the emetic effect have precluded their clinical use against malaria. However, their antimalarial potency makes them attractive substances as leads for developing new types of chemotherapeutic antimalarial drugs. Thus, we have evaluated the in vitro antimalarial activity of the analogues of febrifugine (1) and isofebrifugine (2). The activities of the analogues derived from Df-1 (3) and Df-2 (4), condensation products of 1 and 2 with acetone, respectively, were also obtained. The 3"-keto derivative (7, EC50 = 2.0 x 10(-8) M) of 1 was found to exhibit potential antimalarial activity with high selectivity against P. falciparum in vitro. The in vitro activities of the reduction product (8, EC50 = 2.0 x 10-8 M) of 1 at C-2' and its cyclic derivatives 9 and 10 (EC50 = 3.7 x 10(-9) and 8.6 x 10(-9) M, respectively) were found to be strongly active and selective. Additionally, the Dess-Martin oxidation product of 3 was found to be strongly active with high selectivity against P. falciparum. A structure-activity relationship study (SAR) demonstrates that the essential role played by the 4-quinazolinone ring in the appearance of activity and the presence of a 1"-amino group and C-2', C-3" O-functionalities are crucial in the activity of 1. For 7, 8, and 9, prepared as racemic forms, an in vivo study has also been conducted.

    DOI: 10.1021/jm010448q

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  • Synthesis, Fe(II)-induced degradation, and antimalarial activities of 1,5-diaryl-6,7-dioxabicyclo[3.2.2]nonanes: direct evidence for nucleophilic O-1,2-aryl shifts

    M Kamata, M Ohta, K Komatsu, HS Kim, Y Wataya

    TETRAHEDRON LETTERS   43 ( 11 )   2063 - 2067   2002年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    1,5-Diaryt-6.7-dioxabicyclo[3.2.2]nonanes 1a-d (1a: Ar=p-FC6H4, 1b: Ar=Ph. 1e: Ar=p-MeC6H4. 1d: Ar=pMeOC(6)H(4)) were prepared by a modified method of photo-electron transfer oxygenation. and the reactions of 1 with FeBr2 were investigated under various conditions. The Fe(Il)-induced degradation of 1 afforded various rearrangement products and fragmentation products through competitive single electron transfer (SET) and Lewis acid pathways. Direct evidence for the O-1,2-aryl shift was obtained by the isolation of rearrangement products. 1-aryloxy-5-aryl-8-oxabicyclo[3.2.1]octanes 8. The degradation mechanism was proposed and the in vitro antimalarial activities were also evaluated. (C) 2002 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0040-4039(02)00166-1

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  • Synthesis and notable antimalarial activity of acyclic peroxides, 1-(alkyldioxy)-1-(methyldioxy)cyclododecanes

    Y Hamada, H Tokuhara, A Masuyama, M Nojima, HS Kim, K Ono, N Ogura, Y Wataya

    JOURNAL OF MEDICINAL CHEMISTRY   45 ( 6 )   1374 - 1378   2002年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Of several bis(alkyldioxy)alkanes and the related acyclic peroxides prepared in this study, 1,1-bis(methyldioxy)cyclododecane showed the most notable antimalarial activity particularly in vivo (almost a half of that of artemisinin).

    DOI: 10.1021/jm010473w

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  • New Neplanocin Analogues. 12. Alternative Synthesis and Antimalarial Effect of (6‘R)-6‘-C-Methylneplanocin A, a Potent AdoHcy Hydrolase Inhibitor

    Satoshi Shuto, Noriaki Minakawa, Satoshi Niizuma, Hye-Sook Kim, Yusuke Wataya, Akira Matsuda

    Journal of Medicinal Chemistry   45 ( 3 )   748 - 751   2002年1月

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    出版者・発行元:American Chemical Society (ACS)  

    DOI: 10.1021/jm010374i

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  • New Neplanocin Analogues. 12. Alternative Synthesis and Antimalarial Effect of (6‘R)-6‘-C-Methylneplanocin A, a Potent AdoHcy Hydrolase Inhibitor

    Satoshi Shuto, Noriaki Minakawa, Satoshi Niizuma, Hye-Sook Kim, Yusuke Wataya, Akira Matsuda

    Journal of Medicinal Chemistry   45 ( 3 )   748 - 751   2002年1月

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    出版者・発行元:American Chemical Society (ACS)  

    DOI: 10.1021/jm010374i

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  • Fe(II)-mediated fragmentation of 1,4-diaryl-2,3-dioxabicyclo[2.2.2]octanes through competitive single electron transfer pathway and Lewis acid pathway

    M Kamata, T Kudoh, J Kaneko, HS Kim, Y Wataya

    TETRAHEDRON LETTERS   43 ( 4 )   617 - 620   2002年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Reactions of 1, 4-diaryl-2,3-dioxabicyclo[2.2.2]octanes 1a-d (1a: Ar=p-FC6H4, 1b: Ar=Ph, 1e: Ar=p-MeC6H4, 1d: Ar=p-MeOC6H4) with FeBr2 in THF afforded 1,4-diarylbutan-1,4-diones 2a-d and 1,4-diaryl-7-oxabicyclo[2.2.1]heptanes 3a d. On the other hand, 4-aryl-3-cyclohexenones 4c-d and p-substituted phenols 5c-d were obtained in the reactions of 1c-d with FeBr2 in CH2Cl2. A new fragmentation mechanism involving an electrophilic oxyl radical 1,5-substitution and a nucleophilic O-1,2-aryl shift is proposed based on the product analysis. In addition, the in vitro antimalarial activities of 1a-d were tested. (C) 2002 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0040-4039(01)02201-8

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  • Rhodacyanine dyes as antimalarials. 1. Preliminary evaluation of their activity and toxicity 査読

    Takasu K, Inoue H, Kim H.-S, Suzuki M, Shishido T, Wataya Y, Ihara M

    Journal of Medicinal Chemistry   45 ( 5 )   995 - 998   2002年

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  • Simple isoquinoline and benzylisoquinoline alkaloids as potential antimicrobial, antimalarial, cytotoxic, and anti-HIV agents

    K Iwasa, M Moriyasu, Y Tachibana, HS Kim, Y Wataya, W Wiegrebe, KF Bastow, LM Cosentino, M Kozuka, KH Lee

    BIOORGANIC & MEDICINAL CHEMISTRY   9 ( 11 )   2871 - 2884   2001年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Twenty-six simple isoquinolines and 21 benzylisoquinolines were tested for antimicrobial, antimalarial, cytotoxic, and anti-HIV activities. Some simple isoquinoline alkaloids were significantly active in each assay, and may be useful as lead compounds for developing potential chemotherapeutic agents. These compounds include 13 (antimicrobial), 25, 26, and 42 (antimalarial), 13 and 25 (cytotoxic), and 28 and 29 (anti-HIV). A quaternary nitrogen atom of isoquinolium or dihydroisoquinolinium type may contribute to enhanced potency in the first three types of activities. In contrast, anti-HIV activity was found with tetrahydroisoquinoline and 6,7-dihydroxyisoquinolium salts. (C) 2001 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0968-0896(01)00154-7

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  • Yingzhaosu A analogues: synthesis by the ozonolysis of unsaturated hydroperoxides, structural analysis and determination of anti-malarial activity

    T Tokuyasu, A Masuyama, M Nojima, KJ McCullough, HS Kim, Y Wataya

    TETRAHEDRON   57 ( 28 )   5979 - 5989   2001年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Ozone-mediated cyclization of a series of unsaturated hydroperoxides 7, prepared from dienes 2, afforded the corresponding yingzhaosu A analogues 9 in moderate to high yield. X-Ray crystallographic analysis of two yingzhaosu A analogues, endo-9f and 13, showed that the 2,3-dioxabicyclo[3,3,1]nonane system adopts a chair-boat arrangement. Subsequent treatment of endoperoxides 9 with Ag2O/MeI afforded the expected methyldioxy-substituted cyclic peroxides 14, several of which showed notable anti-malarial activity against P. falciparum in vitro. (C) 2001 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0040-4020(01)00557-9

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  • Synthesis and antimalarial activity of novel medium-sized 1,2,4,5-tetraoxacycloalkanes

    HS Kim, Y Nagai, K Ono, K Begum, Y Wataya, Y Hamada, K Tsuchiya, A Masuyama, M Nojima, KJ McCullough

    JOURNAL OF MEDICINAL CHEMISTRY   44 ( 14 )   2357 - 2361   2001年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    CsOH- or Ag2O-mediated cycloalkylation of (alkylidene)bisperoxides 3 and 1,n.-dihaloalkanes (n = 3-8) provided the corresponding medium-sized 1,2,4,5-tetraoxacycloalkanes 4-8 in moderate yields. Subsequent evaluation of the antimalarial activity of the cyclic peroxides 4-8 in vitro and in vivo revealed that 1,2,6,7-tetraoxaspiro [7.11]nonadecane 4a has considerable potential as a new, inexpensive, and potent antimalarial drug.

    DOI: 10.1021/jm010026g

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  • Synthesis and antimalarial activity of febrifugine derivatives

    Y Takeuchi, M Koike, K Azuma, H Nishioka, H Abe, HS Kim, Y Wataya, T Harayama

    CHEMICAL & PHARMACEUTICAL BULLETIN   49 ( 6 )   721 - 725   2001年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    The regioisomers (2a,b) of the piperidine ring of febrifugine (1a) and isofebrifugine (1b) were synthesized from 4-allyl-3-piperidone (5). Reduction of 5 afforded a mixture of the trans and cis alcohols (6a,b) without diastereoselectivity: this result differentiated it from the reduction of 2-allyl-3-piperidone (14), The antimalarial activity of 2a,b and related compounds was tested.

    DOI: 10.1248/cpb.49.721

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  • Antimalarial and cytotoxic activities of bicycle[6.4.0] dodecenones

    H Fujishima, H Takeshita, M Toyota, HS Kim, Y Wataya, M Tanaka, T Sasaki, M Ihara

    CHEMICAL & PHARMACEUTICAL BULLETIN   49 ( 5 )   572 - 575   2001年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Biological evaluations of bicyclo[6.4.0]dodecenone derivatives on antimalarial activity in vitro against Plasmodium falciparum and cytotoxicity against human KB cells were made. (+/-)-(1R*,4S*,7R*,8S*)-4-tert-Butyl-dimethylsiloxy-5,5-dimethlyl-1-methyl-9-methylene-7-phenylbicyclo[6.4.0]dodec-2,11-dien-10-10-one (15) exhibited potent antimalarial activity, whereas (+/-)-(1R*,7R*,8S*)-1-methyl-9-methylene-7-phenylsulfonybicyclo-[6.4.0]dodec-2,11-dien-10-one (14) showed significant cytotoxic activity in human KB cells. Both 14 and 15 possess, as a structural character, the exo-methylene moiety in their 6-membered ring of the 8-6 fused ring system.

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  • A homologue of N-ethylmaleimide-sensitive factor in the malaria parasite Plasmodium falciparum is exported and localized in vesicular structures in the cytoplasm of infected erythrocytes in the brefeldin A-sensitive pathway

    M Hayashi, S Taniguchi, Y Ishizuka, HS Kim, Y Wataya, A Yamamoto, Y Moriyama

    JOURNAL OF BIOLOGICAL CHEMISTRY   276 ( 18 )   15249 - 15255   2001年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    N-Ethylmaleimide-sensitive factor (NSF) and its homologues play a central role in vesicular trafficking in eukaryotic cells. We have identified a NSF homologue in Plasmodium falciparum (PfNSF), The reported PfNSF gene sequence (GenBank(TM) accession number CAB10575) indicated that PfNSF comprises 783 amino acids with a calculated molecular weight of 89,133, The overall identities of its gene and amino acid sequences with those of rat NSF are 50.9 and 48.8%, respectively. Reverse transcription-polymerase chain reaction analysis and Northern blotting with total P, falciparum RNA indicated expression of the PfNSF gene. Polyclonal. antibodies against a conserved region of NSF specifically recognized an 89-kDa polypeptide in the parasite cells. After homogenization of the parasite cells, similar to 90% of an 89-kDa polypeptide is associated with particulate fraction, suggesting membrane-bound nature of PfNSF. PfNSF was present within both the parasite cells and the vesicular structure outside of the parasite cells, The export of PfNSF outside of the parasite cells appears to occur at the early trophozoite stage and to terminate at the merozoite stage. The export of PfNSF is inhibited by brefeldin A, with 9 muM causing 50% inhibition. Immuno-electromicroscopy indicated that intracellular PfNSF was associated with organelles such as food vacuoles and that extracellular PfNSF was associated with vesicular structures in the erythrocyte cytoplasm, These results indicate that PfNSF expressed in the malaria parasite is exported to the extracellular space and then localized in intraerythrocytic vesicles in a brefeldin A-sensitive manner. It is suggested that a vesicular transport mechanism is involved in protein export targeted to erythrocyte membranes during intraerythrocytic development of the malaria parasite.

    DOI: 10.1074/jbc.M011709200

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  • Synthesis of a novel artemisinin analogue having potent antimalarial activity

    K Takasu, R Katagiri, Y Tanaka, M Toyota, HS Kim, Y Wataya, M Ihara

    HETEROCYCLES   54 ( 2 )   607 - +   2001年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    An artemisinin analogue containing 1,2,4-trioxane structure was designed and synthesized. The compound exhibited significant and selective in vitro antimalarial activity.

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  • Asymmetric synthesis of (+)-febrifugine and (+)-isofebrifugine using yeast reduction

    Y Takeuchi, K Azuma, K Takakura, H Abe, HS Kim, Y Wataya, T Harayama

    TETRAHEDRON   57 ( 7 )   1213 - 1218   2001年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The antimalarial agents febrifugine (D-1) and isofebrifugine (D-2) were synthesized from chiral 3-piperidinol (D-4), which was asymmetrically prepared by the yeast reduction of 3-piperidone derivatives (DL-3), with dynamic optical resolution. (C) 2001 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0040-4020(00)01109-1

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  • Novel guaianoids, nardoguaianone A〜D, from Nardostachys chinensis roots and their antinociceptive and antimalarial activities.

    Takaya, T, Takeuji, Y, Akasaka, M, Nakagawasai, O, Tadano, T, Kisara, K, Kim, H.-S, Wataya, Y, Niwa, M, Oshima, Y

    Tetrahedron,   56 ( 39 )   7673 - 7678   2000年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/S0040-4020(00)00681-5

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  • Synthesis of novel ferrocenyl sugars and their antimalarial activities

    T Itoh, S Shirakami, N Ishida, Y Yamashita, T Yoshida, HS Kim, Y Wataya

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   10 ( 15 )   1657 - 1659   2000年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The synthesis of twelve types of novel ferrocenyl sugars and their biological properties towards the malaria parasite (P. falciparum) and mouse cancer cell (FM3A) are described. (C) 2000 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0960-894X(00)00313-9

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  • Synthesis, crystal structure and antimalarial activity of functionalized spiro-1,2,4,5-tetraoxacycloalkanes from unsaturated hydroperoxy peracetals

    Y Nonami, T Tokuyasu, A Masuyama, M Nojima, KJ McCullough, HS Kim, Y Wataya

    TETRAHEDRON LETTERS   41 ( 23 )   4681 - 4684   2000年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Treatment of unsaturated hydroperoxy peracetals with bis(sym-collidine)iodine(I) hexafluorophosphate affords a series of iodine-containing spiro-1,2,4,5-tetraoxacycloalkane derivatives in high yield. In addition, ozonolysis of unsaturated hydroperoxy peracetals in AcOH-CH2Cl2 also results in the formation of spirol,2,4,5-tetraoxacycloalkanes. Two of the new compounds, 3-methyl-3-methyldioxy-1,2,6,7-tetraoxaspiro[7.11]nonadecane and dimethyl-4-iodo-1,2,6,7-tetraoxaspiro[7.11]nonadecane, exhibit significant in vitro antimalarial activity against P. falciparum with EC50 values of ca. 10(-7) M. (C) 2000 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0040-4039(00)00688-2

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  • Synthesis and anti-malarial activity of yingzhaosu A analogues from unsaturated hydroperoxy acetals

    T Tokuyasu, A Masuyama, M Nojima, HS Kim, Y Wataya

    TETRAHEDRON LETTERS   41 ( 17 )   3145 - 3148   2000年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Ozonolysis of a vinyl ether 2, prepared from dihydrocarvone 1 (a 1:4 mixture of cis- and trans-isomer), in methanol gave two isomeric unsaturated hydroperoxy acetals cis- and trans-3. Iodonium ion- or ozone-mediated cyclizations of the hydroperoxide cis-3 gave the corresponding yingzhaosu A analogues 4 and 6 in moderate yields. The peroxide 8, obtained by the Ag2O-mediated methylation of 6, showed notable anti-malarial activity in vitro (IC50=1.0x10(-7) M). (C) 2000 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0040-4039(00)00372-5

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  • Potent in vivo antimalarial activity of 3,15-di-O-acetylbruceolide against Plasmodium berghei infection in mice

    Hye-Sook Kim, Yasuharu Shibata, Naoko Ko, Naomi Ikemoto, Yuki Ishizuka, Nobutoshi Murakami, Masanori Sugimoto, Motomasa Kobayashi, Yusuke Wataya

    Parasitology International   48 ( 3 )   271 - 274   2000年1月

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    記述言語:英語  

    The antimalarial activity of the O-acylated bruceolide derivative, 3,15-di-O-acetylbruceolide, was evaluated against Plasmodium berghei in vivo. The concentration of 3,15-di-O-acetylbruceolide required for 50% suppression (ED50) of P. berghei in mice was 0.46±0.06 mg/kg/day, whereas bruceolide was only half as effective as 3,15-di-O-acetylbruceolide. Two antimalarial drugs used clinically, chloroquine and artemisinin, demonstrated only low activity corresponding to 1/4 and 1/12 of the ED50 value of 3,15-di-O-acetylbruceolide, respectively. These results may be helpful in the design of better chemotherapeutic bruceolides against falciparum malaria. Copyright (C) 2000 Elsevier Science Ireland Ltd.

    DOI: 10.1016/S1383-5769(99)00023-9

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  • Synthesis, crystal structure and antimalarial activity of novel 1,2,5,6-tetraoxacycloalkanes from 2,3-dihydroperoxy-2-phenylnorbornane

    Kevin J. McCullough, Yuji Nonami, Araki Masuyama, Masatomo Nojima, Hye-Sook Kim, Yusuke Wataya

    Tetrahedron Letters   40 ( 51 )   9151 - 9155   1999年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier Ltd  

    Photooxygenation of 2-phenylnorbornene 1 in the presence of 30% aqueous hydrogen peroxide in acetonitrile afforded the labile 1,2-bis-hydroperoxide 3 which could be cycloalkylated to provide the tricyclic peroxides 5, albeit in low yield, on treatment with silver oxide and a 1,ω-diiodoalkane. Trimethylsilylation of 3, followed by TMSOTf-catalyzed cyclocondensation with carbonyl compounds led to the formation of the tricyclic peroxides 8 containing a 1,2,4,5-tetroxepane structure. The structures of two novel tricyclic peroxides 5a and 8a were unambiguously determined by the X-ray crystallographic analysis.

    DOI: 10.1016/S0040-4039(99)01944-9

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  • New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite

    Y Takaya, H Tasaka, T Chiba, K Uwai, M Tanitsu, HS Kim, Y Wataya, M Miura, M Takeshita, Y Oshima

    JOURNAL OF MEDICINAL CHEMISTRY   42 ( 16 )   3163 - 3166   1999年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Febrifugine (1) and isofebrifugine (2), isolated from the roots of Dichroa febrifuga Lour. (Chinese name: Chang Shan), are active principles against malaria. Adducts of 1 and 2 with acetone, Df-l (3) and Df-2 (4), respectively, were obtained using silica gel and acetone. They showed high activity against P. falciparum malaria in vitro. Compound 3 was found to be equally effective against P. berghei in vivo as the clinically used drug chloroquine, whereas 4 showed only 1/24 of the activity of 3. Metabolism studies of these compounds revealed that compound 4 is readily metabolized in mouse liver. Accordingly, the dose of 4 must be higher than that of 3 to attain blood levels sufficient for a favorable therapeutic effect.

    DOI: 10.1021/jm990131e

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  • Synthesis and antimalarial activity of cyclic peroxides, 1,2,4,5,7-pentoxocanes and 1,2,4,5-tetroxanes

    HS Kim, Y Shibata, Y Wataya, K Tsuchiya, A Masuyama, M Nojima

    JOURNAL OF MEDICINAL CHEMISTRY   42 ( 14 )   2604 - 2609   1999年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    A variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. In both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. For some cyclic peroxides, which were found to be highly effective in vitro, the study in vivo has been also conducted.

    DOI: 10.1021/jm990014j

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  • A colorimetric DNA diagnostic method for falciparum malaria and vivax malaria: A field trial in the Solomon Islands

    M Arai, K Kunisada, HS Kim, H Miyake, C Mizukoshi, T Kakutani, A Yamane, S Nakagami, S Kawai, H Nakano, F Kawamoto, Y Wataya

    NUCLEOSIDES & NUCLEOTIDES   15 ( 1-3 )   719 - 731   1996年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MARCEL DEKKER INC  

    We have developed a colorimetric assay, ''microtiter plate-hybridization'', for the detection of malaria parasites Plasmodium falciparum and P. vivax in human blood, in which the target DNA sequences (18S small subunit ribosomal RNA gene) amplified by polymerase chain reaction (PCR) are hybridized with the species-specific probes immobilized on a microtiter well, This assay system was tested in Guadalcanal, Solomon Islands, where malaria is highly endemic. We obtained blood samples by finger puncture from 130 asymptomatic donors. Among the 130 samples, 30 (23 %) were P. falciparum positive, 28 (22 %) were P. vivax positive, and 8 (6 %) were mixed infections, The results of our DNA diagnostic method showed good correlation with those of acridine orange microscopy.

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  • Species-specific PCR detection of malaria parasites by microtiter plate hybridization: Clinical study with malaria patients

    M. Kimura, H. Miyake, H. S. Kim, M. Tanabe, M. Arai, S. Kawai, A. Yamane, Y. Wataya

    Journal of Clinical Microbiology   33 ( 9 )   2342 - 2346   1995年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A simple and convenient PCR method that amplifies the 18S rRNA genes has been developed for the purpose of detecting and differentiating four species causing malaria in humans. The advantage of the assay is that the biotinylated PCR product is visualized following hybridization with specific probes which are immobilized on plate wells (microtiter plate hybridization). This method has been previously evaluated in a field study and was found to be sensitive and specific for the detection of Plasmodium falciparum and Plasmodium vivax. In the current study, the microtiter plate hybridization PCR method was evaluated by using blood specimens from malaria patients. All of 36 cases of falciparum malaria, 26 of 27 cases of vivax malaria, all of 11 cases of ovale malaria, and 2 cases of malariae malaria were diagnosed species specifically by the PCR method. There were four smear-negative, PCR- positive cases that seemed to correspond to the convalescent stage of malaria. In contrast, 30 cases for which the diagnosis of malaria has been excluded on the basis of microscopy and clinical courses showed negative PCR results. By comparing parasite densities and PCR results following antimalarial treatment of some patients, it was revealed that the PCR results largely paralleled the parasite densities and that PCR could detect as few as 10 parasites per μl of blood. We conclude that this PCR method is highly sensitive and specific for the detection of all four parasite species and can serve as a useful supplement to microscopy for the clinical management of malaria.

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書籍等出版物

  • 抗原虫薬 医学大辞典(プロメディカー)v.3)

    南山堂  2007年 

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  • 病原微生物検出情報、

    厚生労働省発行  2002年 

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  • 「誰にでもわかる遺伝子検査」検査と技術・増刊号

    検査と技術・増刊号、  2002年 

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  • LABEAM 感染症ニュースレター

    ABEAM 感染症ニュースレター  2002年 

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  • 現代医療

    現代医療  2002年 

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  • DNA diagnosis of Malaria in Gradal Canal, Solomon islands

    Malaria Research in Solomon Island 

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  • DNA diagnosis of Malaria in Gradal Canal, Solomon islands

    Malaria Research in Solomon Island 

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MISC

  • マラリア小胞体局在性カルシウム結合タンパク質の大腸菌を用いた高発現とその特性解析

    平岡 修, 高島 康秀, 坂本 沙祐里, 杉山成, 森田将之, 綿矢有佑, 金恵淑

    就実大学薬学雑誌 = The Shujitsu University journal of pharmaceutical sciences   1   42 - 50   2014年

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    記述言語:日本語   出版者・発行元:就実大学薬学部「就実大学薬学雑誌」編集委員会  

    CiNii Article

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  • 薬剤耐性マラリアに対する新規治療薬開発の現況 (特集 感染症医薬品開発の現況) -- (感染症医薬品開発の現況と今後の展望)

    金 惠淑, 佐藤 聡, 森田 将之

    最新医学   67 ( 11 )   2614 - 2620   2012年11月

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    記述言語:日本語   出版者・発行元:最新医学社  

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  • Molecular mechanisms of apoptosis induced by 3'-ethynylcytidine.

    Yusuke Wataya, Tomoharu Naito, Akira Sato, Akiko Hiramoto, Yukio Kitade, Takuma Sasaki, Akira Matsuda, Masakazu Fukushima, Hye Sook Kim

    Nucleic acids symposium series (2004)   291 - 292   2009年12月

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    1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)cytosine (3'-Ethynylcytidine; ECyd), a ribonucleoside analog, has a potent cytotoxic activity against cancer cells. We have investigated the cancer-cell death induced by ECyd, focusing on its molecular mechanisms. In ECyd-treated cells, RNase L is activated and involved in c-jun NH(2)-terminal kinase (JNK) phosphorylation, followed by induction of mitochondria-dependent apoptosis. The mechanism of JNK phophorylation by RNase L was unknown. To investigate the mechanism, we performed the identification of RNase L-binding partners by proteomic approach using co-immunoprecipitation and mass spectrometry. We found that RNase L was associated with a protein (we named it Protein-190). At the same time, we observed that Protein-190 was amply phosphorylated. Furthermore, the participation of Protein-190 in the ECyd-induced apoptosis was supported by a knockdown experiment using small interfering RNA (siRNA). Thus, the number of ECyd-induced apoptotic cells was drastically decreased when Protein-190 was knocked-down. These results indicated Protein-190 as a regulator in apoptosis, and provide the possibility for a new clinical target in cancer chemotherapy.

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  • 新しい抗マラリア薬の開発研究。

    金 惠淑, 綿矢 有佑

    新規素材探索-医薬品リード化合物・食品素材を求めて「監修・上村大輔」。シーエムシー出版社。   1081 - 114   2008年

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  • Molecular mechanisms in two cell death-types, necrosis and apoptosis, induced by 5-fluoro-2’-deoxyuridine.

    Sato, A, Satake, A, Hiramoto, A, Miyazaki, E, Okamatsu, A, Nakama, K, Hiraoka, O, Miyake, T, Kim, H.-S, Wataya, Y

    Nucleic Acids Symposium Ser.,   52   627 - 628   2008年

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  • 抗マラリア薬。

    綿矢 有佑, 金 惠淑

    ファルマシア   44 ( 4 )   32 - 36   2008年

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  • A novel apoptotic pathway of 3'--Ethynylcytidine(ECyd) involving the inhibition of RNA synthesis -The possibility of RNase L activated pathway as a target of ECyd-.

    Naito, T, Yokogawa, T, Kim, H.-S, Masuda, A, Sasaki, T, Fukushima, M, Kitade, Y, Wataya, Y

    Nucleic Acids Sympo. Ser.,   51   2007年

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  • 最近の抗マラリア薬の開発状況。

    金 惠淑

    病原微生物検出情報、厚生労働省発行   vol. 28, No 1,9-10, 2007   2007年

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  • 最近の抗マラリア薬の開発状況。

    金 惠淑

    病原微生物検出情報、厚生労働省発行   vol. 28, No 1,9-10, 2007   2007年

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  • Proteome and transcriptome analysis of cell death induced by 5-fluoro-2ユ-deoxyuridine.

    Sato, A, Miyazaki, E, Satake, A, Hiramoto, A, hiraoka, O, Miyake, T, Kim, H.-S, Wataya, Y

    Nucleic Acids Sympo. Ser., 51 (in press).   51   2007年

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  • Proteome and transcriptome analysis of 5-fluoro-2'-deoxyuridine- induced cell death mechanisims.

    Sato, A, Miyazaki, E, Satake, A, Hiramoto, A, Hiraoka, O, Miyake, T, Kim, H.-S. am, Wataya, Y

    Nucleic Acids Sympo. Ser.,   2006年

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  • 5.抗マラリア薬の開発:過去ー現在ー未来 。

    綿矢 有佑, 金 惠淑

    実験医学   vol. 23 (17), 209-215, 2005.   2005年

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  • 原虫症におけるDNA診断。治療学 (Biomedicine and therapeutics),

    金 惠淑, 綿矢 有佑

    37(6), 55-59, 2003.   37(6), 55-59, 2003.   2003年

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  • 抗原虫薬。

    木村幹男, 金 惠淑, 綿矢有佑

    臨床と微生物、増刊号、   Vol. 30, No. 10, 621-630, 2003.   2003年

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  • マラリアの新しい検査法。

    金 惠淑, 綿矢 有佑, 木村幹男

    最新医学、   58(11)、118-122、2003。   2003年

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  • マラリアのゲノム診断

    綿矢有佑, 金 惠淑

    現代医療,   34 (5), 161-166,   2002年

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  • (13)感染症ーマラリア。「誰にでもわかる遺伝子検査」

    綿矢有佑, 金 惠淑

    検査と技術・増刊号   Vol. 30, No. 10, 1057-1059,   2002年

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講演・口頭発表等

  • ネクローシスとアポトーシスの切替え制御機構の解析

    佐藤 聡, 金 惠淑, 益谷 美都子, 綿矢 有佑, 田沼 靖一

    日本薬学会年会要旨集  2017年3月  (公社)日本薬学会

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    開催年月日: 2017年3月

    記述言語:日本語  

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  • ネクローシスとアポトーシスの細胞死選択におけるmicroRNA351の役割

    佐藤 聡, 金 惠淑, 益谷 美都子, 綿矢 有佑, 田沼 靖一

    日本生化学会大会プログラム・講演要旨集  2016年9月  (公社)日本生化学会

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    開催年月日: 2016年9月

    記述言語:日本語  

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  • ネクローシスとアポトーシスの細胞死マーカーの探索

    佐藤 聡, 金 惠淑, 綿矢 有佑, 益谷 美都子, 田沼 靖一

    日本薬学会年会要旨集  2016年3月  (公社)日本薬学会

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    開催年月日: 2016年3月

    記述言語:日本語  

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  • ネクローシスとアポトーシスを制御するMicroRNAの探索研究

    佐藤 聡, 大見 拓也, 山本 朗央, 金 惠淑, 益谷 美都子, 田沼 靖一, 綿矢 有佑

    日本薬学会年会要旨集  2015年3月  (公社)日本薬学会

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    開催年月日: 2015年3月

    記述言語:日本語  

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  • 細胞がネクローシスで死ぬかアポトーシスで死ぬかを決定づける因子の探索研究(Analysis of switching mechanisms in two cell-death types, necrosis and apoptosis)

    佐藤 聡, 益谷 美都子, 早津 彦哉, 金 惠淑, 綿矢 有佑

    日本癌学会総会記事  2013年10月  日本癌学会

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    開催年月日: 2013年10月

    記述言語:英語  

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  • ロダシアニン系色素化合物の抗マラリア作用機序の解析

    佐内仁美, 鈴木健一, 井原正隆, 高須清誠, 金恵淑, 綿矢有佑

    日本薬学会年会要旨集  2005年3月5日 

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    開催年月日: 2005年3月5日

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  • 抗マラリア活性を持つβ‐カルボリン類の合成

    下釜翼, 高須清誠, 金恵淑, 綿矢有佑, 井原正隆

    日本薬学会年会要旨集  2004年3月5日 

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    開催年月日: 2004年3月5日

    記述言語:日本語  

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  • β‐カルボリンを基盤とする抗マラリア活性物質の開発研究

    下釜翼, 高須清誠, KIM H‐S, 綿矢有佑, 井原正隆

    天然薬物の開発と応用シンポジウム講演要旨集  2003年11月1日 

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    開催年月日: 2003年11月1日

    記述言語:日本語  

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  • β‐カルボリン型アルカロイドをリードする抗マラリア剤の開発

    高須清誠, 下釜翼, SAIIN C, 金恵淑, 綿矢有佑, 井原正隆

    日本薬学会年会要旨集  2003年3月5日 

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    開催年月日: 2003年3月5日

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  • DLC理論に基づくロダシアニン色素の抗マラリア活性 (IV) コンビナトリアル合成によるライブラリー構築

    高須清誠, 伊上博史, 金恵淑, 綿矢有佑, 井原正隆

    日本薬学会年会要旨集  2001年3月5日 

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    開催年月日: 2001年3月5日

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  • DLC理論に基づくロダシアニン色素の抗マラリア活性 (V) A,B,およびC環それぞれにおける構造活性相関

    伊上博史, 高須清誠, 金恵淑, 綿矢有佑, 井原正隆

    日本薬学会年会要旨集  2001年3月5日 

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    開催年月日: 2001年3月5日

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  • 抗マラリア活性ロダシアニン系色素の創製研究

    高須清誠, 伊上博史, 井原正隆, KIM H‐S, 綿矢有佑, 宍戸忠夫

    メディシナルケミストリーシンポジウム・日本薬学会医薬化学部会年会講演要旨集  2000年11月8日 

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    開催年月日: 2000年11月8日

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  • アルテミシニン類縁体の合成と抗マラリア活性

    高須清誠, 片桐留理子, 田中優子, 井原正隆, 金恵淑, 綿矢有佑

    日本薬学会年会要旨集  2000年3月5日 

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    開催年月日: 2000年3月5日

    記述言語:日本語  

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  • DLC理論に基づくロダシアニン系色素の抗マラリア活性

    高須清誠, 井原正隆, 綿矢有佑, 鈴木真, 宍戸忠夫, KIM H‐S

    メディシナルケミストリーシンポジウム・日本薬学会医薬化学部会年会講演要旨集  1999年11月2日 

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    開催年月日: 1999年11月2日

    記述言語:日本語  

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  • 5-Fluoro-2「-deoxyuridineが誘導する細胞死分子機構の解析ミネクローシスとアポトーシスのオミクス解析-

    日本薬学会 第128年会,  2008年 

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  • マラリア新規治療薬開発の基盤研究。

    第49回日本熱帯医学会・第23回日本国債保健医療学会(合同学会合同シンポジウム)、  2008年 

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  • 環状過酸化化合物の抗マラリア作用とその作用機構の解析.

    第7回分子寄生虫・マラリア研究フォーラム, 2008年10月10日-11日,  2008年 

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  • 環状過酸化化合物N-89投与時のマンソン住血吸虫プロテオーム解析.

    第2回蠕虫研究会, 2008年11月7日-8日,  2008年 

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  • 5-Fluoro-2-deoxyuridineが誘導する細胞死分子機構の解析〜ネクローシスとアポトーシスのオミクス解析〜.

    第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会, 2008年12月9日-12日,  2008年 

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  • Molecular mechanisms in two cell death-types, necrosis and apoptosis, induced by 5-fluoro-2「-deoxyuridine.

    Joint Symposium of 18th International Roundtable on Nucleosides, Nucleotides and Nucleic Acids and 35th International Symposium on Nucleic Acids Chemistry, September, 2008,  2008年 

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  • Proteome analysis of schistosoma mansoni in the treatment of the infected animals with a new antischistosomal endoperoxide, N-89.

    8th Awaji International Forum on Infection and Immunity, September, 2008,  2008年 

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  • New antimalarial drug development research -antimalarial synthetic endoperoxides-

    XVIIth International Congress for Tropical Medicine and Malaria, September, 2008,  2008年 

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  • New Antimalarial Drug Development Research -Antiamlarial Synthetic Endoperoxides-.

    大韓寄生虫学会第71回学術集談会、  2008年 

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  • New Antimalarial Drug Development Research -Antiamlarial Synthetic Endoperoxides-.

    第3回国際セミナー、July , 2008.  2008年 

     詳細を見る

  • Analysis of target molecules for antimalarial endoperoxide.

    XVIIth International Congress for Tropical Medicine and Malaria, September, 2008,  2008年 

     詳細を見る

  • Proteome analysis of Schistosoma mansoni treat with new antiparasitic endoperoxide.

    XVIIth International Congress for Tropical Medicine and Malaria, September, 2008,  2008年 

     詳細を見る

  • 環状過酸化化合物のマンソン住血吸虫に対する効果~Proteomicsによるアプローチ~

    日本薬学会 第128年会,  2008年 

     詳細を見る

  • Proteome analysis of differentially expressed proteins in Endoperoxide treated Schistosoma mansoni.

    77回日本寄生虫学会,  2008年 

     詳細を見る

  • New Antimalarial Drug Development Research -Antimalarial Synthetic Endoperoxides-.

    International Research in Infectious Diseases Meeting,  2008年 

     詳細を見る

  • 5-Fluoro-2「-deoxyuridineが誘導する細胞死のオミクス解析.

    第12回がん分子標的治療研究会総会, 2008年6月,  2008年 

     詳細を見る

  • Proteome and transcriptome analysis of cell death induced by 5-fluoro-2ユ-deoxyuridine.

    第5回国際核酸化学シンポジウム、  2007年 

     詳細を見る

  • New Antimalarial Drug Development Research。

    The 3rd International Zoonosis Seminar, November 29-30,2007,  2007年 

     詳細を見る

  • 環状過酸化化合物のマンソン住血吸虫に対する効果~Proteomicsによるアプローチ~。

    第6回分子寄生虫・マラリア研究フォーラム、2007年10月27〜28日、  2007年 

     詳細を見る

  • 新規抗マラリア薬の開発研究—環状過酸化化合物の抗マラリア活性と体内動態。

    第6回分子寄生虫・マラリア研究フォーラム、  2007年 

     詳細を見る

  • 抗マラリア作用を有する新規環状過酸化化合物の標的分子の探索。

    第6回分子寄生虫・マラリア研究フォーラム、2007年10月27〜28日  2007年 

     詳細を見る

  • A novel apoptotic pathway of 3'-Ethynylcytidine(ECyd) involving the inhibition of RNA synthesis -The possibility of RNase L activated pathway as a target of ECyd-。

    第5回国際核酸化学シンポジウム、  2007年 

     詳細を見る

  • Mechanism analysis of new antimalarial endoperoxides using proteomics

    日本寄生虫学会  2007年 

     詳細を見る

  • 新規抗マラリア薬の開発--環状過酸化化合物:in vitroからin vivoへ--

    日本寄生虫学会  2007年 

     詳細を見る

  • 広範囲抗寄生虫薬の開発のための標的治療の分子基盤の確立

    第1回特定領域班会議  2007年 

     詳細を見る

  • 広範囲抗寄生虫薬の開発のための標的治療の分子基盤の確立

    第2回班会議  2007年 

     詳細を見る

  • Detection of malaria parasite by Microtiter plate hybridization in field collected Anopheles mosquitoes from a malaria endemic area of Bangladesh

    日本薬学会  2007年 

     詳細を見る

  • RNA合成阻害剤3ユ-Ethynylcytidine(ECyd)のRNase L活性化を介したアポトーシス誘導機構

    日本薬学会  2007年 

     詳細を見る

  • 新規抗マラリア薬の開発-環状過酸化化合物の抗マラリア活性と体内動態-

    日本寄生虫学会  2007年 

     詳細を見る

  • 新規抗腫瘍ヌクレオシドアナログ 3'-Ethynylcytidine の代謝活性化酵素 uridine/cytidine kinase 2 遺伝子のSNP解析とその発現量解析

    日本薬学会  2007年 

     詳細を見る

  • 新規抗マラリア薬の開発ー環状過酸化化合物を中心に

    日本寄生虫学会  2006年 

     詳細を見る

  • Genomic analysis of mefloquine-resis新規抗マラリア薬の開発 --環状過酸化化合物:in vitroからin vivoへ--

    新技術研究会  2006年 

     詳細を見る

  • サル・重症マラリア疾患モデルによる新規抗マラリア薬の治療効果試験

    東日本寄生虫学会  2006年 

     詳細を見る

  • New Antimalarial Drug Development Research in Japan –2 -Antimalarial Activity of Endoperoxide

    ICOPA XI  2006年 

     詳細を見る

  • 熱帯熱マラリア原虫におけるメフロキン耐性化機構の解析

    日本薬学会  2006年 

     詳細を見る

  • New antimalarial endoperoxide, action and resistance analysis

    日本薬学会  2006年 

     詳細を見る

  • 5-Fluoro-2-deoxyuridineが誘導する細胞死分子機構の解明.

    日本薬学会 第126年会,  2006年 

     詳細を見る

  • Proteome analysis and application to study Plasmodium falciparum drug resistance mechanism

    日本寄生虫学会  2006年 

     詳細を見る

  • 新規抗マラリア薬の創製研究

    日本薬学会  2006年 

     詳細を見る

  • Proteome analysis of cell death induced by 5-Fluoro-2’-deoxyuridine

    forum cheju  2006年 

     詳細を見る

  • Proteome Analysis of Plasmodium falciparum induced by Antimalarial endoperoxide

    forum cheju  2006年 

     詳細を見る

  • Proteome and transcriptome analysis of 5-fluoro-2-deoxyuridine-induced cell death mechanisms.

    33th Symposium on Nucleic Acids Chemistry,  2006年 

     詳細を見る

  • Antimalarial Function Analysis of New Antiamlarial Endoperoxides

    第6回あわじしま感染症・免疫フォーラム  2006年 

     詳細を見る

  • 抗マラリア作用を有する新規環状過酸化化合物の標的分子の探索 ムプロテオーム解析を中心にー

    第5回分子寄生虫・マラリア研究フォーラム  2006年 

     詳細を見る

  • 新規抗マラリア薬の開発 ム環状過酸化化合物の抗マラリア活性と体内動態—

    第5回分子寄生虫・マラリア研究フォーラム  2006年 

     詳細を見る

  • 熱帯熱マラリア原虫のメフロキン耐性に関与するpfmdr1遺伝子の機能解析。

    日本薬学会 第125年会, 2005年3月28-31,  2005年 

     詳細を見る

  • 新規抗マラリア薬の開発ム環状過酸化物の抗マラリア活性と体内動態ム。

    日本薬学会 第125年会, 2005年3月28-31,  2005年 

     詳細を見る

  • 3ユ-Ethynylcytidine(ECyd)の代謝活性化酵素uridine/cytidine kinase2のSNP解析。

    日本薬学会 第125年会, 2005年3月28-31,  2005年 

     詳細を見る

  • 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl) cytocine (ECyd)の抗腫瘍メカニズムの解析。

    日本薬学会 第125年会, 2005年3月28-31,  2005年 

     詳細を見る

  • 5-Fluoro-2-deoxyuridine (FUdR)が誘導する細胞死分子機構の解明: NecrosisまたはApoptosisの誘導メカニズムについて.

    日本薬学会 第125年会, 2005年3月28-31,  2005年 

     詳細を見る

  • 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl) cytosine (ECyd, TAS-106)の抗腫瘍メカニズムの解析。

    日本薬学会 第125年会, 2005年3月28-31,  2005年 

     詳細を見る

  • ロダシアニン系化合物の抗マラリア作用機序の解析。

    日本薬学会 第125年会, 2005年3月28-31,  2005年 

     詳細を見る

  • New Antimalarial Drug Development Research in Japan –2 -Antimalarial Activity of Endoperoxide-

    16th International congress for Tropical Medicine and malaria, September 11-15, 2005  2005年 

     詳細を見る

  • 中瀬由佳理、谷川菜津希、田中朝子、金 惠淑、綿矢有佑、Jinming Wu、益山新樹、野島正朋、川合 覚。

    第44回日本熱帯医学会、2005年10月14-15  2005年 

     詳細を見る

  • 新規抗マラリア薬の創製研究—環状過酸化物を中心に—

    第74回日本寄生虫学会大会、2005年4月8-9  2005年 

     詳細を見る

  • メフロキン耐性熱帯熱マラリア原虫の耐性化機構の解析

    第74回日本寄生虫学会大会、2005年4月8-9  2005年 

     詳細を見る

  • Antimalarial Drug Development Research - New Antimalarial Endoperoxides

    3rd Cheju forum, June 3-5, 2005  2005年 

     詳細を見る

  • New Antimalarial Drug Development Research in Japan –1

    16th International congress for Tropical Medicine and malaria, September 11-15, 2005  2005年 

     詳細を見る

  • 谷川菜津希、中瀬由佳理、田中朝子、金 惠淑、綿矢有佑、Jinming Wu、益山新樹、野島正朋、川合 覚、三谷公里栄、片岡弘行

    第4回寄生虫・マラリア研究フォーラム、2005年11月5-6  2005年 

     詳細を見る

  • 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl) cytosine (ECyd, TAS-106)の抗腫瘍メカニズムの解析

    日本薬学会  2003年 

     詳細を見る

  • 新規抗マラリア薬の創製研究—環状過酸化物を中心に—

    日本寄生虫学会  2003年 

     詳細を見る

  • 熱帯熱マラリア原虫におけるメフロキン耐性化機構の解析

    日本寄生虫学会  2003年 

     詳細を見る

  • New Antimalarial Drug Development esearch -Johzan analogs and endoperoxides-

    沖縄若手フォーラム  2003年 

     詳細を見る

  • 有機合成環状過酸化物の新しい抗マラリア薬としての試み

    日本薬学会  2003年 

     詳細を見る

  • 5-Fluoro-2'-deoxyuridine (FUdR) が誘導する細胞死分子機構の解析:necrosisまたはapoptosisの誘導メカニズムについて

    日本薬学会  2003年 

     詳細を見る

  • Anticancer Mechanisms of 1 - ( 3 - C - ethynyl - b -D- ribo-pentofuranosyl) cytosine (ECyd, TAS-106)

    がん分子標的研究会  2003年 

     詳細を見る

  • Genomic analysis of mefloquine-resistant mechanism of human malaria parasites

    淡路フォーラム  2003年 

     詳細を見る

  • DNA diagnosis of malaria using microtiter-plate hybridization method

    日本熱帯医学会  2003年 

     詳細を見る

  • 熱帯熱マラリア原虫におけるメフロキン耐性化機構の解析

    日本寄生虫学会西日本支部大会  2003年 

     詳細を見る

  • 新規抗マラリア剤の開発—-環状過酸化物の抗マラリア活性—

    日本寄生虫学会  2002年 

     詳細を見る

  • New Antimalarial Drug Development against Drug Resistant Malaria

    淡路フォーラム  2002年 

     詳細を見る

  • 新規抗マラリア剤の開発—-環状過酸化物の抗マラリア活性

    日本薬学会  2002年 

     詳細を見る

  • Microtiter-Plate Hybridization 法を用いたマラリアの DNA 診断

    日本薬学会第122年会、  2002年 

     詳細を見る

  • 新規抗マラリア剤の開発―-環状過酸化物の抗マラリア活性―

    第71回日本寄生虫学会大会  2002年 

     詳細を見る

  • Analysis of pfmdr1 gene in mefloquine-resistant Plasmodium falciparum

    71回日本寄生虫学会大会、  2002年 

     詳細を見る

  • 新規抗マラリア薬の創製研究

    岡山県シード化合物の研究報告会  2002年 

     詳細を見る

  • 新規抗マラリア剤の開発—-環状過酸化物の抗マラリア活性—

    日米医学研究協力会  2002年 

     詳細を見る

  • 新規抗マラリア剤の開発―-環状過酸化物の抗マラリア活性―

    日米医学寄生虫疾患部門部会国内研究会議  2002年 

     詳細を見る

  • 新規抗マラリア剤の開発―-環状過酸化物の抗マラリア活性―

    日本薬学会第122年会、  2002年 

     詳細を見る

  • マウス肝s9-mix により得られたfebrifugine 代謝物の合成

    日本薬学会第122年会  2002年 

     詳細を見る

  • Mechanisms of Cell death induced by 5-fluoro-2'-deoxyuridine (FUdR)

    核酸化学シンポジウム  2002年 

     詳細を見る

  • 熱帯熱マラリア原虫におけるメフロキン耐性機構の解析

    マラリア研究会  2002年 

     詳細を見る

  • Analysis of single nucleotide polymorphisms in uridine/cytidine kinase gene encoding metabolic enzyme of 3'-ethynylcytidine

    核酸化学シンポジウム  2002年 

     詳細を見る

  • analysis of drug-resistant mechanism of mefloquine

    核酸化学シンポジウム  2002年 

     詳細を見る

  • Anticancer mechanism of 1-(3-c-ethynyl-b-D- ribofentofuranosyl)cytosine (ECyd,Tas 106)

    核酸化学シンポジウム  2002年 

     詳細を見る

  • メフロキン耐性熱帯熱マラリア原虫のpfmdr 1遺伝子の解析

    日本薬学会第121年会  2001年 

     詳細を見る

  • 新規抗マラリア薬の開発 ― 環状過酸化物の抗マラリア作用

    日本薬学会第121年会  2001年 

     詳細を見る

  • 新規抗マラリア剤の開発―-環状過酸化物の抗マラリア活性―

    第70回日本寄生虫学会大会  2001年 

     詳細を見る

  • 環状過酸化物の抗マラリア作用

    第121年回日本薬学会(Workshop)  2001年 

     詳細を見る

  • Antimalarial endoperoxides

    Gordon Research Conferences (Malaria)  2001年 

     詳細を見る

  • 3'-Ethynylcytidine ( ECyd ) が誘導する細胞死の分子作用機序

    第28回核酸化学シンポジウム  2001年 

     詳細を見る

  • Microtiter-Plate Hybridization 法を用いたマラリアの DNA 診断

    日本薬学会第40回中国四国支部大会、  2001年 

     詳細を見る

  • メフロキン耐性熱帯熱マラリア原虫の Pfmdr 1 遺伝子の解析

    第28回核酸化学シンポジウム  2001年 

     詳細を見る

  • 新規抗マラリア薬の創製研究 - 環状過酸化物の抗マラリア作用 -

    日本薬学会第40回中国四国支部大会  2001年 

     詳細を見る

  • 熱帯熱マラリア原虫におけるメフロキン耐性機構の分子生物学的解析

    日本薬学会第40回中国四国支部大会  2001年 

     詳細を見る

  • 新規抗マラリア薬の作用機序の解析 I

    日本薬学会第40回中国四国支部大会  2001年 

     詳細を見る

  • 新規抗マラリア薬の作用機序の解析 II

    日本薬学会第40回中国四国支部大会  2001年 

     詳細を見る

  • メフロキン耐性熱帯熱マラリア原虫のpfmdr 1遺伝子の解析

    第70回日本寄生虫学会大会  2001年 

     詳細を見る

  • 日本における抗マラリア薬開発研究の現状

    第70回日本寄生虫学会大会  2001年 

     詳細を見る

  • nalysis of pfmdr1 gene in mefloquine-resistant Plasmodium falciparum

    第42回日本熱帯医学会  2001年 

     詳細を見る

  • 新規抗マラリア剤の開発 ―環状過酸化物の抗マラリア活性―

    第42回日本熱帯医学会  2001年 

     詳細を見る

  • 新規抗マラリア薬の開発 — 環状過酸化物の抗マラリア作用

    第41回日本熱帯医学会、  2000年 

     詳細を見る

  • 環状過酸化物の抗マラリア活性

    日本薬学会第39回中国四国支部大会、  2000年 

     詳細を見る

  • 新規抗マラリア薬の開発 I — 環状過酸化物の抗マラリア作用

    日本薬学会第120年会、  2000年 

     詳細を見る

  • Development of New Antimalarial Drugs - In Vitro And In Vivo Antimalarial Activity of Endoperoxides.

    第69回日本寄生虫学会大会、  2000年 

     詳細を見る

  • Mefloquine耐性熱帯熱マラリア原虫のpfmdr1遺伝子の解析

    第 8 回分子寄生虫学 Workshop,  2000年 

     詳細を見る

  • 沖縄産 Acanthella 属海綿由来の Kalihinol 関連化合物の構造とその抗マラリア活性に ついて

    日本薬学会第119年会、  1999年 

     詳細を見る

  • Febrifugine 誘導体の抗マラリア活性

    日本薬学会第119年会、  1999年 

     詳細を見る

  • 生薬・常山成分誘導体の抗マラリア活性

    日本薬学会第119年会、  1999年 

     詳細を見る

  • Febrifugine 誘導体の合成

    日本薬学会第119年会  1999年 

     詳細を見る

  • シンプルイソキノリンアルカロイドの生物活性

    日本薬学会第119年会、  1999年 

     詳細を見る

  • 新規抗マラリア剤の開発ー環状過酸化物の抗マラリア活性

    第40回日本熱帯医学会・第14回日本国際保険医療学会、  1999年 

     詳細を見る

  • 環状過酸化物の in vivo 抗マラリア活性

    第40回日本熱帯医学会・第14回日本国際保険医療学会、  1999年 

     詳細を見る

  • Antisense oligonucleotideの抗マラリア作用機序の検討

    第40回日本熱帯医学会・第14回日本国際保険医療学会  1999年 

     詳細を見る

  • 新規抗マラリア剤の開発ー環状過酸化物の抗マラリア活性

    第40回日本生化学会、  1999年 

     詳細を見る

  • Antimalarial products from Dichroa febrifuga (JOH-ZAN)

    第68回日本寄生虫学会大会、  1999年 

     詳細を見る

  • Studies of antisense oligonucleotide-effects against P. falciparum

    第68回日本寄生虫学会大会、  1999年 

     詳細を見る

  • 新規抗マラリア剤の開発ー環状過酸化物の抗マラリア活性

    第68回日本寄生虫学会大会、  1999年 

     詳細を見る

  • 新規抗マラリア剤の開発ー生薬・常山の抗マラリアアルカロイドについて

    第40回日本熱帯医学会・第14回日本国際保険医療学会、  1999年 

     詳細を見る

  • Antisense oligonucleotideの抗マラリア作用機序の検討

    日本薬学会第119年会、  1999年 

     詳細を見る

▼全件表示

受賞

  • 女性賞

    2018年11月   日本熱帯医学会   難治性感染症制御に向けた創薬研究

     詳細を見る

  • 平成19 年度科学技術分野の文部科学大臣表彰 若手科学者賞

    2007年4月   文部科学省   薬剤耐性に有効な新規抗マラリア薬の創製研究

     詳細を見る

  • ベンチャービジネスプランコンテスト 審査員特別賞

    2003年11月   岡山県 ベンチャープラザ岡山2003   マラリアの検査システムの確立と全国ネットワークの構築

     詳細を見る

  • 奨励賞

    2003年3月   日本寄生虫学会   新規抗マラリア薬・環状過酸化化合物の抗マラリア活性と作用機序の解析

     詳細を見る

 

担当授業科目

  • くすりの話 (2021年度) 第2学期  - 月3~4

  • 分子生物学3 (2021年度) 第1学期  - 木5,木6

  • 分子生物学3 (2021年度) 第1学期  - 木5,木6

  • 分子生物学4 (2021年度) 第2学期  - 木5,木6

  • 分子生物学4 (2021年度) 第2学期  - 木5,木6

  • 創薬研究を支える生命科学 (2021年度) 第3学期  - 木5~6

  • 医薬品分子標的学 (2021年度) 特別  - その他

  • 医薬品分子標的学I(演習・実習) (2021年度) 特別  - その他

  • 医薬品分子標的学I(講義・演習) (2021年度) 特別  - その他

  • 医薬品分子標的学II(演習・実習) (2021年度) 特別  - その他

  • 医薬品分子標的学II(講義・演習) (2021年度) 特別  - その他

  • 医薬品情報学1 (2021年度) 第1学期  - 火3~4

  • 医薬品情報学1 (2021年度) 第1学期  - 火3~4

  • 医薬品情報学2 (2021年度) 第2学期  - 火3~4

  • 医薬品情報学2 (2021年度) 第2学期  - 火3~4

  • 微生物学 (2021年度) 3・4学期  - 金3,金4

  • 微生物学 (2021年度) 3・4学期  - 金3,金4

  • 特殊講義(国際連携薬学人材育成プログラム) (2021年度) 特別  - その他

  • 特殊講義(国際連携薬学人材育成プログラム) (2021年度) 特別  - その他

  • 特殊講義(国際連携薬学人材育成プログラム) (2021年度) 特別  - その他

  • 特殊講義(国際連携薬学人材育成プログラム) (2021年度) 特別  - その他

  • 生命科学2 (2021年度) 後期  - その他

  • 薬学基礎実習Ⅲ (2021年度) 第2学期  - その他6~9

  • 薬学基礎実習Ⅲ (2021年度) 第2学期  - その他6~9

  • 薬学基礎実習Ⅲ (2021年度) 第2学期  - その他6~9

  • 薬学基礎実習Ⅲ (2021年度) 第2学期  - その他6~9

  • くすりの話 (2020年度) 第2学期  - 月3,月4

  • 分子生物学Ⅱ (2020年度) 1・2学期  - 木5,木6

  • 分子生物学3 (2020年度) 第1学期  - 木5,木6

  • 分子生物学3 (2020年度) 第1学期  - 木5,木6

  • 分子生物学4 (2020年度) 第2学期  - 木5,木6

  • 分子生物学4 (2020年度) 第2学期  - 木5,木6

  • 分子細胞生物学II (2020年度) 1・2学期  - 木5,木6

  • 創薬研究を支える生命科学 (2020年度) 第3学期  - 木5,木6

  • 医薬品分子標的学 (2020年度) 特別  - その他

  • 医薬品分子標的学I(演習・実習) (2020年度) 特別  - その他

  • 医薬品分子標的学I(講義・演習) (2020年度) 特別  - その他

  • 医薬品分子標的学II(演習・実習) (2020年度) 特別  - その他

  • 医薬品分子標的学II(講義・演習) (2020年度) 特別  - その他

  • 医薬品情報学 (2020年度) 1・2学期  - 火3,火4

  • 医薬品情報学1 (2020年度) 第1学期  - 火3,火4

  • 医薬品情報学1 (2020年度) 第1学期  - 火3,火4

  • 医薬品情報学2 (2020年度) 第2学期  - 火3,火4

  • 医薬品情報学2 (2020年度) 第2学期  - 火3,火4

  • 微生物学 (2020年度) 3・4学期  - 金3,金4

  • 微生物学 (2020年度) 3・4学期  - 金3,金4

  • 微生物学 (2020年度) 3・4学期  - 金3,金4

  • 特殊講義(国際連携薬学人材育成プログラム) (2020年度) 特別  - その他

  • 特殊講義(国際連携薬学人材育成プログラム) (2020年度) 特別  - その他

  • 生命科学2 (2020年度) 特別  - その他

  • 薬学基礎実習Ⅲ (2020年度) 第2学期  - その他

  • 薬学基礎実習Ⅲ (2020年度) 第2学期  - その他

▼全件表示