2021/04/08 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

  • Malariology

  • 医薬品開発学

  • Infectious diseases therapy

  • drug development

  • マラリア学

  • 感染症治療学

研究分野

  • ライフサイエンス / 薬理学

  • ライフサイエンス / 薬系衛生、生物化学

 

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 

     詳細を見る

  • 病原微生物検出情報、

    厚生労働省発行  2002年 

     詳細を見る

  • 「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 

     詳細を見る

  • LABEAM 感染症ニュースレター

    ABEAM 感染症ニュースレター  2002年 

     詳細を見る

  • 現代医療

    現代医療  2002年 

     詳細を見る

  • DNA diagnosis of Malaria in Gradal Canal, Solomon islands

    Malaria Research in Solomon Island 

     詳細を見る

  • DNA diagnosis of Malaria in Gradal Canal, Solomon islands

    Malaria Research in Solomon Island 

     詳細を見る

▼全件表示

MISC

  • Potential of synthetic endoperoxides against Trichomonas vaginalis in vitro

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

    PARASITOLOGY INTERNATIONAL66 ( 5 ) 619 - 621   2017年10月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

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

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

    Anti-Cancer Drugs28 ( 7 ) 781 - 786   2017年8月

     詳細を見る

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

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

    VIRUS RESEARCH235   37 - 48   2017年5月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 INTERNATIONAL66 ( 1 ) 917 - 924   2017年2月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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

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

    PARASITOLOGY INTERNATIONAL65 ( 5 ) 494 - 499   2016年10月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 ONE11 ( 4 )   2016年4月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 RESEARCH32 ( 8 ) 2595 - 2608   2015年8月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

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

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

    PARASITOLOGY INTERNATIONAL64 ( 1 ) 113 - 117   2015年2月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 J281 ( 7 ) 1892 - 1900   2014年4月

     詳細を見る

  • 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 CALORIMETRY115 ( 3 ) 2089 - 2097   2014年3月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 ONE8 ( 8 ) e72519   2013年8月

     詳細を見る

    記述言語:英語   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.

    DOI: 10.1371/journal.pone.0072519

    Web of Science

    researchmap

  • 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 Intermediates39 ( 1 ) 127 - 137   2013年1月

     詳細を見る

    記述言語:英語  

    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.

    DOI: 10.1007/s11164-012-0637-3

    Scopus

    researchmap

  • 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 CHEMISTRY16 ( 16 ) 7698 - 7704   2008年8月

     詳細を見る

    記述言語:英語   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.

    DOI: 10.1016/j.bmc.2008.07.010

    Web of Science

    researchmap

  • 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

     詳細を見る

  • 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

     詳細を見る

  • 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 ACIDS27 ( 5 ) 433 - 438   2008年

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • Detection of malaria parasites in mosquitoes from a malaria endemic area Chakaria, Bangladesh.

    Tangin, A, komichi, Y, Wagatsuma, Y, Rashidul, H, Wataya, Y, Kim, H.-S

    Biol. Pharm. Bull.31 ( 4 ) 703 - 708   2008年

     詳細を見る

  • 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

     詳細を見る

  • 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

     詳細を見る

  • 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 RESEARCH100 ( 5 ) 1119 - 1124   2007年4月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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

     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-.

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

    Nucleic Acids Sympo. Ser.,51   2007年

     詳細を見る

  • 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

     詳細を見る

  • 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

     詳細を見る

  • Preparation of Quinoline Hexose Analogs as Novel Chloroquine-Resistant Malaria Treatments (1). Synthesis of 4-Hydroxyquinoline-a-glucosides.

    Suzuki, H, Aly, N, Wataya, Y, Kim, H.-S, Tamai, I, Kita, M, Uemura, D

    Chem. Pharm. Bull.,(In Press).   2007年

     詳細を見る

  • In vitro antimalarial activity of flavonoids and chalcons.

    Lim, S, Kim, H.-S, Lee, D

    Bull. Korean Chem. Soc., 28 (12), 2495-2497, 2007.28 ( 12 ) 2495 - 2497   2007年

     詳細を見る

  • Design, synthesis and in vitro antimalarial activity of spiroperoxides

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

    TETRAHEDRON62 ( 33 ) 7699 - 7711   2006年8月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 LETTERS16 ( 10 ) 2758 - 2760   2006年5月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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

     詳細を見る

  • 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

     詳細を見る

  • 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

     詳細を見る

  • 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

    TETRAHEDRON61 ( 42 ) 9961 - 9968   2005年10月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 COMMUNICATIONS330 ( 4 ) 1168 - 1175   2005年5月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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.,   2005年

     詳細を見る

  • 1,2,4,5-Tetraoxan cycloalkanes: Synthesis and Antimalarial Activity.

    Masuyama, A, Wu, J-M, Nojima, M, Kim, H.-S, Wataya, Y

    Mini-Reviews Med. chem.,   2005年

  • 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

     詳細を見る

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

    Yu, S, Kim, J, Lee, C, Han, J, Lee, J, Kim, H.-S, Hong, J, Kang, S

    Biol. Pharm. Bull.,   2005年

     詳細を見る

  • 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,   2005年

     詳細を見る

  • 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 ACIDS24 ( 3 ) 227 - 232   2005年

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • Synthesis and biological activity of fatty acid conjugate of quinine.

    Kumura, N, Izumi, M, Nakajima, S, Shimizu, S, Kim, H.-S, Wataya, Y, Baba, N

    Biosci. Biotech. Biochem.,   2005年

     詳細を見る

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

    Liu, H, Jin, H, Zhang, Q, Wu, Y, Kim, H.-S, Wataya, Y

    Chinese J. Chem.,   2005年

     詳細を見る

  • 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.,   2005年

     詳細を見る

  • 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 LETTERS13 ( 22 ) 3963 - 3965   2003年11月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 ETHNOPHARMACOLOGY86 ( 2-3 ) 249 - 252   2003年6月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 CHEMISTRY5 ( 3 ) 211 - 214   2003年5月

     詳細を見る

    記述言語:英語   出版者・発行元:AMER CHEMICAL SOC  

    DOI: 10.1021/cc020119z

    Web of Science

    researchmap

  • 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 CHEMISTRY46 ( 10 ) 1957 - 1961   2003年5月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 CHEMISTRY46 ( 4 ) 638 - 641   2003年2月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

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

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

    Chem Pharm Bull,   2003年

     詳細を見る

  • In vitro antimalarial activity of metalloporphyrins against Plasmodium falciparum.

    Begum, K, Kim, H.-S, Kumar, V, Stojiljkovic, I, Wataya, Y

    Parssitol. Res.,   2003年

     詳細を見る

  • Metabolites of febrifugine and its synthetic analog Df-1 by mouse liver S9 and their antimalarial activity against Plasmodium malaria parasite.

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

    J. Med. Chem.,   2003年

     詳細を見る

  • 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

     詳細を見る

  • 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

     詳細を見る

  • Synthesis of antimalarial Yingzhaosu A analogues by the peroxidation of dienes with Co(II)/O2/Et3SiH.

    Tokuyasu, T, Kunikawa, S, Abe, M, Masuyama, A, Nojima, M, Kim, H.-S, Wataya, Y

    J. Org. Chem.,   2003年

     詳細を見る

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

    Park. H, Kim, M, Jeon, B, Kim, T, Kim, Y, Ahn, J, Kwon, D.-Y, Takaya, Y, Wataya, Y, Kim, H.-S

    Biol. Pharm. Bull.,   2003年

     詳細を見る

  • 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 Chemotherapy9 ( 3 ) 254 - 256   2003年

     詳細を見る

    記述言語:英語   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

    Scopus

    PubMed

    researchmap

  • 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

     詳細を見る

  • 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 CHEMISTRY45 ( 12 ) 2563 - 2570   2002年6月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 CHEMISTRY45 ( 6 ) 1374 - 1378   2002年3月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • 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 CHEMISTRY45 ( 6 ) 1374 - 1378   2002年3月

     詳細を見る

    記述言語:英語   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

    Web of Science

    researchmap

  • New neplanocin analogs 12. An alternative synthesis of (6'R)-6'-C-methylneplanocin A (RMNPA), a novel potent anti-malarial agent.

    Shuto, S, Niizuma, S, Minakawa, N, Kim, H.-S, Wataya, Y, Matsuda, A

    J. Med. Chem.,   2002年

     詳細を見る

  • The antimalarial activity of yingzhaosu A analogues.

    Kim, H.-S, Begum, K, Ogura, N, Wataya, Y, Tokuyasu, T, Masuyama, A, Nojima, M, McCullough, K.J

    J. Med. Chem.,   2002年

     詳細を見る

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

    Kamata, M, Satoh, C, Kim, H.-S, Wataya, Y

    Tetrahedron Letters,   2002年

  • Rhodacyanine dyes as antimalarials. 1.Antimalarial activity and toxicity of rhodacyanine dyes.

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

    J. Med. Chem., 2002 (in press).   2002年

     詳細を見る

  • Rhodacyanine dyes as antimalarials. 1.Antimalarial activity and toxicity of rhodacyanine dyes.

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

    J. Med. Chem.   2002年

     詳細を見る

  • 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

     詳細を見る

  • 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.

    Kamata, M, Ohta, M, Komatsu,K, Kim, H.-S, Wataya, Y

    Tetrahedron letters,   2002年

  • 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.

    Kamata, M, Kudoh, T, Kaneko, J, Kim, H.-S, Wataya, Y

    Tetrahedron letters,   2002年

  • 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.

    Kamata, M, Kudoh, T, Kaneko, J, Kim, H.-S, Wataya, Y

    Tetrahedron letters,   2002年

  • (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

     詳細を見る

  • 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.

    Kamata, M, Ohta, M, Komatsu,K, Kim, H.-S, Wataya, Y

    Tetrahedron letters,   2002年

  • New neplanocin analogs 12. An alternative synthesis of (6'R)-6'-C-methylneplanocin A (RMNPA), a novel potent anti-malarial agent.

    Shuto, S, Niizuma, S, Minakawa, N, Kim, H.-S, Wataya, Y, Matsuda, A

    J. Med. Chem.,   2002年

     詳細を見る

  • Antimalarial and cytotoxic activities of bicyclo[6.4.0]dodecanes.

    Fujishima, H, Takeshita, H, Toyota, M, Kim, H.-S, Wataya, Y, Tanaka, M, Sasaki, T, Ihara, M

    Chem. Pharm. Bull.,   2001年

     詳細を見る

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

    Takeuchi, Y, Azuma, K, Takakura, K, Abe, H, Kim, H.-S, Wataya, Y, Harayama, T

    Tetrahedron,   2001年

  • Synthesis of a novel artemisinin analog having potent antimalarial activity.

    Takasu,K, Katagiri, R, Tanaka. Y, Toyoda, M, Kim, H.-S, Wataya, Y, Ihara, M

    Heterocycles,   2001年

     詳細を見る

  • Synthesis and antimalarial activity of febrifugine derivatives.

    Takeuchi, Y, Koike, M, Azuma, K, Nishioka, H, Abe, H, Kim, H.-S, Wataya, Y, Harayama, T

    Chem., Pharm. Bull.,   2001年

     詳細を見る

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

    Iwasa, K, Moriyasu, M, Tachibana, Y, Kim, H.-S, Wataya, Y, Wiegrebe, W, Bastow, K. F, Cosentino, L. M, Kozuka, M, Lee, K.-H

    Bioorg. Med. Chem.,   2001年

  • Yingzhaosu A Analogues: Synthesis by the ozonolyis of unsaturated hydroperoxides, structural analysis and determination of anti-malarial activity.

    Tokuyasu, T, Masuyama, A, Nojima. M, McCullough, K. J, Kim, H.-S, Wataya, Y

    Tetrahedron,   2001年

  • 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 erythrocyte in the brefeldin A-sensitive pathway.

    Hayashi, M, Taniguchi, S. Ishizuka, Y, Kim, H.-S, Wataya, Y, Yamamoto, S, Moriyama, Y

    J. Biol. Chem.,   2001年

     詳細を見る

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

    Kim, H.-S, Nagai, Y, Ono, K, Begum, K, wataya, Y, Hamada, Y, Tsuchiya, K, Masuyama, A, Nojima, M, McCullough, K. J

    J. Med. Chem.,   2001年

     詳細を見る

  • Novel guaiane endoperoxides, nardoguaianone A-D, from Nardostachys chinensis roots and their antinociceptive and antimalarial activities

    Yoshiaki Takaya, Yoshie Takeuji, Megumi Akasaka, Osamu Nakagawasai, Takeshi Tadano, Kensuke Kisara, Hye-Sook Kim, Yusuke Wataya, Masatake Niwa, Yoshiteru Oshima

    Tetrahedron56 ( 39 ) 7673 - 7678   2000年9月

     詳細を見る

    記述言語:英語   出版者・発行元:Elsevier Ltd  

    Four novel guaianoids, nardoguaianone A, B, C and D, were isolated from Nardostachys chinensis roots. The structures were elucidated by spectral means and chemical transformation. Antinociceptive activities of the constituents of N. chinensis, including some of the above novel compounds, were investigated by the formalin test. As a result, it was revealed that nardoguaianone A and D showed activity at the second phase of pain induced by formalin injection. (C) 2000 Elsevier Science Ltd.

    DOI: 10.1016/S0040-4020(00)00682-7

    Scopus

    researchmap

  • Novel guaiane endoperoxides, nardoguaianone A-D, from Nardostachys chinensis roots and their antinociceptive and antimalarial activities

    Yoshiaki Takaya, Yoshie Takeuji, Megumi Akasaka, Osamu Nakagawasai, Takeshi Tadano, Kensuke Kisara, Hye-Sook Kim, Yusuke Wataya, Masatake Niwa, Yoshiteru Oshima

    Tetrahedron56 ( 39 ) 7673 - 7678   2000年9月

     詳細を見る

    記述言語:英語   出版者・発行元:Elsevier Ltd  

    Four novel guaianoids, nardoguaianone A, B, C and D, were isolated from Nardostachys chinensis roots. The structures were elucidated by spectral means and chemical transformation. Antinociceptive activities of the constituents of N. chinensis, including some of the above novel compounds, were investigated by the formalin test. As a result, it was revealed that nardoguaianone A and D showed activity at the second phase of pain induced by formalin injection. (C) 2000 Elsevier Science Ltd.

    DOI: 10.1016/S0040-4020(00)00682-7

    Scopus

    researchmap

  • Synthesis of novel ferrocenyl sugars and their antimalarial activities

    Toshiyuki Itoh, Shohei Shirakami, Nanae Ishida, Yukiko Yamashita, Takashi Yoshida, Hye-Sook Kim, Yusuke Wataya

    Bioorganic and Medicinal Chemistry Letters10 ( 15 ) 1657 - 1659   2000年8月

     詳細を見る

    記述言語:英語  

    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

    Scopus

    PubMed

    researchmap

  • Synthesis of novel ferrocenyl sugars and their antimalarial activities

    Toshiyuki Itoh, Shohei Shirakami, Nanae Ishida, Yukiko Yamashita, Takashi Yoshida, Hye-Sook Kim, Yusuke Wataya

    Bioorganic and Medicinal Chemistry Letters10 ( 15 ) 1657 - 1659   2000年8月

     詳細を見る

    記述言語:英語  

    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

    Scopus

    PubMed

    researchmap

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

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

    Tetrahedron Letters41 ( 23 ) 4681 - 4684   2000年6月

     詳細を見る

    記述言語:英語   出版者・発行元:Elsevier 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 spiro-1,2,4,5-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.

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

    Scopus

    researchmap

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

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

    Tetrahedron Letters41 ( 23 ) 4681 - 4684   2000年6月

     詳細を見る

    記述言語:英語   出版者・発行元:Elsevier 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 spiro-1,2,4,5-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.

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

    Scopus

    researchmap

  • 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 International48 ( 3 ) 271 - 274   2000年1月

     詳細を見る

    記述言語:英語   掲載種別:書評論文,書評,文献紹介等  

    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

    Scopus

    PubMed

    researchmap

  • 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 International48 ( 3 ) 271 - 274   2000年1月

     詳細を見る

    記述言語:英語   掲載種別:書評論文,書評,文献紹介等  

    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

    Scopus

    PubMed

    researchmap

  • 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 International48 ( 3 ) 271 - 274   2000年1月

     詳細を見る

    記述言語:英語   掲載種別:書評論文,書評,文献紹介等  

    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

    Scopus

    PubMed

    researchmap

  • Synthesis ans anti-malarial activity of Yingzhaosu A analogues from unsaturated hydroperoxy acetals.

    Tokuyasu, T, Masuyama, A, Nojima, M, Kim, H.-S, Wataya, Y

    Tetrahedron Letters,   2000年

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

    Nonami, Y, Tokuyasu, T, Masuyama, A, Nojima, M, McCullough, K. J, Kim, H.-S, Wataya, Y

    Tetrahedron Letters,   2000年

  • 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,   2000年

  • A trial for a DNA diagnosis of tertian malaria recently re-emerging in the Republic of Korea using microtiter plate hybridization assay.

    Chai, J-Y, Guk, S-M, Lee, S-H, Park, Y-G, Oh, K-H, Oh, M-D, Kim, H.-S, Wataya, Y

    Am. J Trop. Med. Hyg.,   2000年

     詳細を見る

  • Synthesis of novel ferrocenyl sugars and their antimalarial activities.

    Itoh, T, Shirakami, S, Ishida, N, Yamashita, Y, Yoshida, T, Kim, H.-S, Wataya, Y

    Bioorg. Med. Chem. Lett.   2000年

  • 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 Letters40 ( 51 ) 9151 - 9155   1999年12月

     詳細を見る

    記述言語:英語   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

    Scopus

    researchmap

  • 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 Letters40 ( 51 ) 9151 - 9155   1999年12月

     詳細を見る

    記述言語:英語   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

    Scopus

    researchmap

  • 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 Letters40 ( 51 ) 9151 - 9155   1999年12月

     詳細を見る

    記述言語:英語   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

    Scopus

    researchmap

  • 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 Letters40 ( 51 ) 9151 - 9155   1999年12月

     詳細を見る

    記述言語:英語   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

    Scopus

    researchmap

  • Catalytic asymmetric synthesis of antimalarial alkaloids febrifugine and isofebrifugine and their biological activity

    Shu Kobayashi, Masaharu Ueno, Ritsu Suzuki, Haruro Ishitani, Hye-Sook Kim, Yusuke Wataya

    Journal of Organic Chemistry64 ( 18 ) 6833 - 6841   1999年9月

     詳細を見る

    記述言語:英語  

    Antimalarial alkaloids febrifugine (1) and isofebrifugine (2) were efficiently synthesized from simple achiral starting materials on the basis of the catalytic asymmetric synthesis. The first key reaction was performed using the tin(II)-mediated catalytic asymmetric aldol protocol to afford chiral aldehyde 3 in high yield with high diastereo- and enantioselectivities. The second key step, a Mannich-type reaction, did not give satisfactory results according to the conventional methods. We then developed a novel aqueous Mannich-type three-component reaction of an aldehyde, an amine, and a vinyl ether using a Lewis acid-surfactant combined catalyst (LASC), and the key intermediates 16 and 17 were obtained in high yields. The final coupling reactions of bromoacetone 14 with 4- hydroxyquinazoline were carried out using basic conditions, and successive deprotection gave 1 and 2, respectively, without any isomerization. These- unambiguous total asymmetric syntheses revealed that the absolute configurations of febrifugine and isofebrifugine were not (2'S,3'R) and (2'R,3'R) as reported previously but (2'R,3'S) and (2'S,3'S), respectively (1' and 2'). Finally, antimalarial activities of the synthesized febrifugine and isofebrifugine, and their antipodes, were examined. It was revealed that the activities and selectivities of natural febrifugine and isofebrifugine were much higher than those of the antipodes.

    DOI: 10.1021/jo990877k

    Scopus

    researchmap

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

    Yoshiaki Takaya, Hidehisa Tasaka, Tomoyuki Chiba, Koji Uwai, Masa-Aki Tanitsu, Hye-Sook Kim, Yusuke Wataya, Masatomo Miura, Mitsuhiro Takeshita, Yoshiteru Oshima

    Journal of Medicinal Chemistry42 ( 16 ) 3163 - 3166   1999年8月

     詳細を見る

    記述言語:英語  

    Febrifugine (1) and isofebrifugine (2), isolated from the roots of Dichroa febrifuga Lour. (Chinese name: Chang Shah), are active principles against malaria. Adducts of 1 and 2 with acetone, Df-1 (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

    Scopus

    PubMed

    researchmap

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

    Yoshiaki Takaya, Hidehisa Tasaka, Tomoyuki Chiba, Koji Uwai, Masa-Aki Tanitsu, Hye-Sook Kim, Yusuke Wataya, Masatomo Miura, Mitsuhiro Takeshita, Yoshiteru Oshima

    Journal of Medicinal Chemistry42 ( 16 ) 3163 - 3166   1999年8月

     詳細を見る

    記述言語:英語  

    Febrifugine (1) and isofebrifugine (2), isolated from the roots of Dichroa febrifuga Lour. (Chinese name: Chang Shah), are active principles against malaria. Adducts of 1 and 2 with acetone, Df-1 (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

    Scopus

    PubMed

    researchmap

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

    Hye-Sook Kim, Yasuharu Shibata, Yusuke Wataya, Kaoru Tsuchiya, Araki Masuyama, Masatomo Nojima

    Journal of Medicinal Chemistry42 ( 14 ) 2604 - 2609   1999年7月

     詳細を見る

    記述言語:英語  

    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

    Scopus

    PubMed

    researchmap

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

    Hye-Sook Kim, Yasuharu Shibata, Yusuke Wataya, Kaoru Tsuchiya, Araki Masuyama, Masatomo Nojima

    Journal of Medicinal Chemistry42 ( 14 ) 2604 - 2609   1999年7月

     詳細を見る

    記述言語:英語  

    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

    Scopus

    PubMed

    researchmap

  • Synthesis, crystal structure and anti-malarial activity of novel spiro- 1,2,4,5-tetraoxacycloalkanes

    Kaoru Tsuchiya, Yoshiaki Hamada, Araki Masuyama, Masatomo Nojima, Kevin J. McCullough, Hye-Sook Kim, Yasuharu Shibata, Yusuke Wataya

    Tetrahedron Letters40 ( 21 ) 4077 - 4080   1999年5月

     詳細を見る

    記述言語:英語  

    (Cycloalkylidene)bishydroperoxides 3 react with 1,n-dihaloalkanes (n = 3-6) in the presence of CsOH-H2O in DMF affording the corresponding spiro- 1,2,4,5-tetraoxacycloalkanes 4 in moderate yields. Compound 4ba exhibits significant antimalarial activity in vitro against P. falciparum.

    DOI: 10.1016/S0040-4039(99)00653-X

    Scopus

    researchmap

  • Synthesis, crystal structure and anti-malarial activity of novel spiro- 1,2,4,5-tetraoxacycloalkanes

    Kaoru Tsuchiya, Yoshiaki Hamada, Araki Masuyama, Masatomo Nojima, Kevin J. McCullough, Hye-Sook Kim, Yasuharu Shibata, Yusuke Wataya

    Tetrahedron Letters40 ( 21 ) 4077 - 4080   1999年5月

     詳細を見る

    記述言語:英語  

    (Cycloalkylidene)bishydroperoxides 3 react with 1,n-dihaloalkanes (n = 3-6) in the presence of CsOH-H2O in DMF affording the corresponding spiro- 1,2,4,5-tetraoxacycloalkanes 4 in moderate yields. Compound 4ba exhibits significant antimalarial activity in vitro against P. falciparum.

    DOI: 10.1016/S0040-4039(99)00653-X

    Scopus

    researchmap

  • Cycloprodigiosin hydrochloride obtained from Pseudoalteromonas denitrificans is a potent antimalarial agent

    Hye Sook Kim, Mitsuko Hayashi, Yasuharu Shibata, Yusuke Wataya, Toshihide Mitamura, Toshihiro Horii, Keiko Kawauchi, Hajime Hirata, Seiji Tsuboi, Yoshinori Moriyama

    Biological and Pharmaceutical Bulletin22 ( 5 ) 532 - 534   1999年5月

     詳細を見る

    記述言語:英語   出版者・発行元:Pharmaceutical Society of Japan  

    Cycloprodigiosin hydrochloride (cPrG·HCl) is a stable fluorescent red pigment obtained from the marine bacterium Pseudoalteromonas denitrificans. It was found that the compound was incorporated into Plasmodium falciparum cells upon incubation and exhibited a potent antimalarial activity with the concentration required for 50% of the activity being 11 nM, which is stronger than that of chloroquine, a well-known antimalarial agent. The compound did not affect growth rate of mammalian cells. Antimalarial activity of cPrG·HCl was also observed in vivo. These results indicate that cPrG·HCl is a potent antimalarial drug.

    DOI: 10.1248/bpb.22.532

    Scopus

    PubMed

    researchmap

  • Cycloprodigiosin hydrochloride obtained from Pseudoalteromonas denitrificans is a potent antimalarial agent

    Hye Sook Kim, Mitsuko Hayashi, Yasuharu Shibata, Yusuke Wataya, Toshihide Mitamura, Toshihiro Horii, Keiko Kawauchi, Hajime Hirata, Seiji Tsuboi, Yoshinori Moriyama

    Biological and Pharmaceutical Bulletin22 ( 5 ) 532 - 534   1999年5月

     詳細を見る

    記述言語:英語   出版者・発行元:Pharmaceutical Society of Japan  

    Cycloprodigiosin hydrochloride (cPrG·HCl) is a stable fluorescent red pigment obtained from the marine bacterium Pseudoalteromonas denitrificans. It was found that the compound was incorporated into Plasmodium falciparum cells upon incubation and exhibited a potent antimalarial activity with the concentration required for 50% of the activity being 11 nM, which is stronger than that of chloroquine, a well-known antimalarial agent. The compound did not affect growth rate of mammalian cells. Antimalarial activity of cPrG·HCl was also observed in vivo. These results indicate that cPrG·HCl is a potent antimalarial drug.

    DOI: 10.1248/bpb.22.532

    Scopus

    PubMed

    researchmap

  • Synthesis, Crystal structure and antimalarial activity of novel 1,2,5,6-tetracycloalkanes from 2,3-dihydroperoxy-2-phenylnorbonate.

    McCullough, K. J, Nonami, y, Masuyama, A, Nojima, M, Kim, H.-S, Wataya, Y

    Tetrahedron Letters,   1999年

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

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

    J. Med. Chem.,   1999年

     詳細を見る

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

    Kim, H.-S, Shibata, Y, Wataya, Y, Tsuchiya, K, Masuyama, A, Nojima, M

    J. Med. Chem.,   1999年

     詳細を見る

  • Synthesis and antimalarial activity of dl-deoxyfebrifugine.

    Takeuchi, Y, Tokuda, S, Takagi, T, Koike, M, Abe, H, Harayama, T, Shibata, Y, Kim, H.-S, Wataya, Y

    Heterocycles,   1999年

     詳細を見る

  • Synthetic methods for unsymmetrically-substituted 1,2,4,5-tetroxanes and of 1,2,4,5,7-pentoxocanes.

    Kim, H.-S, Tsuchiya, K, Shibata, Y, Wataya, Y, Ushigoe, Y, Masuyama, A, Nojima, M, McCullough, K. J

    J. Chem. Soc. Perkin Trans., 1,   1999年

     詳細を見る

  • Catalytic asymmetric synthesis of antimalarial alkaloids febrifugine and isofebrifugine and their biological activity. J. Org. Chem., 64(18), 6833-6841, 1999.

    Kobayashi, S, Ueno, M, Suzuki, R, Ishitani, H, Kim, H.-S, Wataya, Y

    J. Org. Chem.,   1999年

     詳細を見る

  • Synthesis, crystal structure and anti-malarial activity of novel spiro-1,2,4,5-tetraoxacycloalkanes.

    Tsuchiya, K, Hamada, Y, Masuyama, A, Nojima, M, McCullough, K. J, Kim, H.-S, Shibata, Y, Wataya, Y

    Tetrahedron Letters,   1999年

  • Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity

    Kinuko Iwasa, Yumi Nishiyama, Momoyo Ichimaru, Masataka Moriyasu, Hye-Sook Kim, Yusuke Wataya, Takao Yamori, Turuo Takashi, Dong-Ung Lee

    European Journal of Medicinal Chemistry34 ( 12 ) 1077 - 1083   1999年

     詳細を見る

    記述言語:英語   出版者・発行元:Elsevier Masson SAS  

    Seventeen quaternary protoberberine alkaloids related to berberine 1 were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the oxygen substituents on rings A, C and D and the position of the oxygen functions on ring D. The position of the oxygen functions on ring D and the type of the oxygen substituents at the C-13 position (ring C) strongly influenced the activity. Shifting the oxygen functions at C-9 and C-10 to C-10 and C-11 on ring D resulted in a significant increase in the activity. Compounds bearing a methylenedioxy function at C-2 and C-3 (ring A) or C-9 and C-10 (ring D) showed higher activity than those which have methoxy groups at the same positions. Introduction of a methoxy group into the C-1 position (ring A) decreased the activity. Replacement of a hydroxy group at C-2 or C-3 (ring A) by a methoxy group led to a reduction in the activity. Displacement of a hydroxy function at C-13 (ring C) by the oxygen substituents such as OMe, OEt, OCOOEt, and OCON(Me)2 reduced the activity. In the same replacement at C-9 (ring D), the activity depended upon the type of the oxygen function. Six protoberberines displayed more potent activity than berberine 1. The activity decreased in the order: 10, 11, 17 and 18 &gt
    7 and 8 &gt
    1.

    DOI: 10.1016/S0223-5234(99)00127-0

    Scopus

    researchmap

  • Structure-activity relationships of quaternary protoberberine alkaloids having antimalarial activity.

    Iwasa, K, Nishiyama, Y, Ichimaru, M, Moriyasu, M, Kim, H.-S, Wataya, Y, Yamori, T, Takashi, T, Lee, D.-U

    Eur. J. Med. Chem.,   1999年

  • Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity

    Kinuko Iwasa, Yumi Nishiyama, Momoyo Ichimaru, Masataka Moriyasu, Hye-Sook Kim, Yusuke Wataya, Takao Yamori, Turuo Takashi, Dong-Ung Lee

    European Journal of Medicinal Chemistry34 ( 12 ) 1077 - 1083   1999年

     詳細を見る

    記述言語:英語   出版者・発行元:Elsevier Masson SAS  

    Seventeen quaternary protoberberine alkaloids related to berberine 1 were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the oxygen substituents on rings A, C and D and the position of the oxygen functions on ring D. The position of the oxygen functions on ring D and the type of the oxygen substituents at the C-13 position (ring C) strongly influenced the activity. Shifting the oxygen functions at C-9 and C-10 to C-10 and C-11 on ring D resulted in a significant increase in the activity. Compounds bearing a methylenedioxy function at C-2 and C-3 (ring A) or C-9 and C-10 (ring D) showed higher activity than those which have methoxy groups at the same positions. Introduction of a methoxy group into the C-1 position (ring A) decreased the activity. Replacement of a hydroxy group at C-2 or C-3 (ring A) by a methoxy group led to a reduction in the activity. Displacement of a hydroxy function at C-13 (ring C) by the oxygen substituents such as OMe, OEt, OCOOEt, and OCON(Me)2 reduced the activity. In the same replacement at C-9 (ring D), the activity depended upon the type of the oxygen function. Six protoberberines displayed more potent activity than berberine 1. The activity decreased in the order: 10, 11, 17 and 18 &gt
    7 and 8 &gt
    1.

    DOI: 10.1016/S0223-5234(99)00127-0

    Scopus

    researchmap

  • Cycloprodigiosin hydrochloride obtained from Pseudoalteromonas denitrificans is a potent antimalarial agent.

    Kim, H.-S, Hayashi, M, Shibata, Y, Wataya, Y, Mitamura, T, Horii, T, Hirata, H, Tsuboi, S, Moriyama, Y

    Biol. Pharm. Bull.,   1999年

     詳細を見る

  • Antimalarial activity of kalihinol A and new relative diterpenoids from the Okinawan sponge, Acanthella sp.

    Hiroaki Miyaoka, Masako Shimomura, Haruko Kimura, Yasuji Yamada, Hye-Sook Kim, Yusuke Wataya

    Tetrahedron54 ( 44 ) 13467 - 13474   1998年10月

     詳細を見る

    記述言語:英語  

    Three new kalihinane diterpenoids Δ9-kalihinol Y (1), 10-epikalihinol I (2) and 5,10-bisisothiocyanatokalihinol G (3) were isolated in the present study along with previously detected kalihinane diterpenoids kalihinol A (4), kalihinene (5) and 6-hydroxykalihinene (6) from the Okinawan marine sponge, Acanthella sp. Kalihinol A (4) was noted to possess remarkable in vitro antimalarial activity.

    DOI: 10.1016/S0040-4020(98)00818-7

    Scopus

    researchmap

  • Antimalarial activity of kalihinol A and new relative diterpenoids from the Okinawan sponge, Acanthella sp.

    Hiroaki Miyaoka, Masako Shimomura, Haruko Kimura, Yasuji Yamada, Hye-Sook Kim, Yusuke Wataya

    Tetrahedron54 ( 44 ) 13467 - 13474   1998年10月

     詳細を見る

    記述言語:英語  

    Three new kalihinane diterpenoids Δ9-kalihinol Y (1), 10-epikalihinol I (2) and 5,10-bisisothiocyanatokalihinol G (3) were isolated in the present study along with previously detected kalihinane diterpenoids kalihinol A (4), kalihinene (5) and 6-hydroxykalihinene (6) from the Okinawan marine sponge, Acanthella sp. Kalihinol A (4) was noted to possess remarkable in vitro antimalarial activity.

    DOI: 10.1016/S0040-4020(98)00818-7

    Scopus

    researchmap

  • Novel antimalarial guaiane-type sesquiterpenoids from Nardostachys chinensis roots

    Yoshiaki Takaya, Ken-Ichi Kurumada, Yoshie Takeuji, Hye-Sook Kim, Yasuharu Shibata, Naomi Ikemoto, Yusuke Wataya, Yoshiteru Oshima

    Tetrahedron Letters39 ( 11 ) 1361 - 1364   1998年3月

     詳細を見る

    記述言語:英語  

    Three guaiane-type sesquiterpenoids, nardoperoxide (1a), isonardoperoxide (2a) and nardoxide (3), were isolated from Nardostachys chinensis roots. Their structures were elucidated by spectral means. Among them, two endoperoxides, nardoperoxide (1a) and isonardoperoxide (2a), showed strong antimalarial activity against Plasmodium falciparum malaria (EC50 1.5 x 10-6 and 6.0 x 10-7 M, respectively).

    DOI: 10.1016/S0040-4039(97)10844-9

    Scopus

    researchmap

  • Novel antimalarial guaiane-type sesquiterpenoids from Nardostachys chinensis roots

    Yoshiaki Takaya, Ken-Ichi Kurumada, Yoshie Takeuji, Hye-Sook Kim, Yasuharu Shibata, Naomi Ikemoto, Yusuke Wataya, Yoshiteru Oshima

    Tetrahedron Letters39 ( 11 ) 1361 - 1364   1998年3月

     詳細を見る

    記述言語:英語  

    Three guaiane-type sesquiterpenoids, nardoperoxide (1a), isonardoperoxide (2a) and nardoxide (3), were isolated from Nardostachys chinensis roots. Their structures were elucidated by spectral means. Among them, two endoperoxides, nardoperoxide (1a) and isonardoperoxide (2a), showed strong antimalarial activity against Plasmodium falciparum malaria (EC50 1.5 x 10-6 and 6.0 x 10-7 M, respectively).

    DOI: 10.1016/S0040-4039(97)10844-9

    Scopus

    researchmap

  • Novel antimalarial guaiane-type sesquiterpenoids from Nardostachys chinensis roots

    Yoshiaki Takaya, Ken-Ichi Kurumada, Yoshie Takeuji, Hye-Sook Kim, Yasuharu Shibata, Naomi Ikemoto, Yusuke Wataya, Yoshiteru Oshima

    Tetrahedron Letters39 ( 11 ) 1361 - 1364   1998年3月

     詳細を見る

    記述言語:英語  

    Three guaiane-type sesquiterpenoids, nardoperoxide (1a), isonardoperoxide (2a) and nardoxide (3), were isolated from Nardostachys chinensis roots. Their structures were elucidated by spectral means. Among them, two endoperoxides, nardoperoxide (1a) and isonardoperoxide (2a), showed strong antimalarial activity against Plasmodium falciparum malaria (EC50 1.5 x 10-6 and 6.0 x 10-7 M, respectively).

    DOI: 10.1016/S0040-4039(97)10844-9

    Scopus

    researchmap

  • Novel antimalarial guaiane-type sesquiterpenoids from Nardostachys chinensis roots

    Yoshiaki Takaya, Ken-Ichi Kurumada, Yoshie Takeuji, Hye-Sook Kim, Yasuharu Shibata, Naomi Ikemoto, Yusuke Wataya, Yoshiteru Oshima

    Tetrahedron Letters39 ( 11 ) 1361 - 1364   1998年3月

     詳細を見る

    記述言語:英語  

    Three guaiane-type sesquiterpenoids, nardoperoxide (1a), isonardoperoxide (2a) and nardoxide (3), were isolated from Nardostachys chinensis roots. Their structures were elucidated by spectral means. Among them, two endoperoxides, nardoperoxide (1a) and isonardoperoxide (2a), showed strong antimalarial activity against Plasmodium falciparum malaria (EC50 1.5 x 10-6 and 6.0 x 10-7 M, respectively).

    DOI: 10.1016/S0040-4039(97)10844-9

    Scopus

    researchmap

  • Anti-malarial activities of acylated bruceolide derivatives

    Nobutoshi Murakarni, Takashi Umezome, Taifo Mahmud, Masanori Sugimoto, Motomasa Kobayashi, Yusuke Wataya, Hye-Sook Kim

    Bioorganic and Medicinal Chemistry Letters8 ( 5 ) 459 - 462   1998年3月

     詳細を見る

    記述言語:英語  

    Several O-acylated derivatives of bruceolide (2) were synthesized and their anti-malarial activities together with selective toxicities were examined. It was found that 3,15-di-O-acetyl- (3c), 3,15-di-O-propionyl- (3d) and 15-O-propionylbruceolide (3b), as well as bruceine B (3a), exhibited potent anti-malarial activities with high selective toxicities.

    DOI: 10.1016/S0960-894X(98)00045-6

    Scopus

    PubMed

    researchmap

  • Anti-malarial activities of acylated bruceolide derivatives

    Nobutoshi Murakarni, Takashi Umezome, Taifo Mahmud, Masanori Sugimoto, Motomasa Kobayashi, Yusuke Wataya, Hye-Sook Kim

    Bioorganic and Medicinal Chemistry Letters8 ( 5 ) 459 - 462   1998年3月

     詳細を見る

    記述言語:英語  

    Several O-acylated derivatives of bruceolide (2) were synthesized and their anti-malarial activities together with selective toxicities were examined. It was found that 3,15-di-O-acetyl- (3c), 3,15-di-O-propionyl- (3d) and 15-O-propionylbruceolide (3b), as well as bruceine B (3a), exhibited potent anti-malarial activities with high selective toxicities.

    DOI: 10.1016/S0960-894X(98)00045-6

    Scopus

    PubMed

    researchmap

  • Anti-malarial activities of acylated bruceolide derivatives

    Nobutoshi Murakarni, Takashi Umezome, Taifo Mahmud, Masanori Sugimoto, Motomasa Kobayashi, Yusuke Wataya, Hye-Sook Kim

    Bioorganic and Medicinal Chemistry Letters8 ( 5 ) 459 - 462   1998年3月

     詳細を見る

    記述言語:英語  

    Several O-acylated derivatives of bruceolide (2) were synthesized and their anti-malarial activities together with selective toxicities were examined. It was found that 3,15-di-O-acetyl- (3c), 3,15-di-O-propionyl- (3d) and 15-O-propionylbruceolide (3b), as well as bruceine B (3a), exhibited potent anti-malarial activities with high selective toxicities.

    DOI: 10.1016/S0960-894X(98)00045-6

    Scopus

    PubMed

    researchmap

  • Anti-malarial activities of acylated bruceolide derivatives

    Nobutoshi Murakarni, Takashi Umezome, Taifo Mahmud, Masanori Sugimoto, Motomasa Kobayashi, Yusuke Wataya, Hye-Sook Kim

    Bioorganic and Medicinal Chemistry Letters8 ( 5 ) 459 - 462   1998年3月

     詳細を見る

    記述言語:英語  

    Several O-acylated derivatives of bruceolide (2) were synthesized and their anti-malarial activities together with selective toxicities were examined. It was found that 3,15-di-O-acetyl- (3c), 3,15-di-O-propionyl- (3d) and 15-O-propionylbruceolide (3b), as well as bruceine B (3a), exhibited potent anti-malarial activities with high selective toxicities.

    DOI: 10.1016/S0960-894X(98)00045-6

    Scopus

    PubMed

    researchmap

  • Antimalarial activity and nucleoside transport inhibitory activity of the triterpenic constituents of Cimicifuga spp.

    Masayuki Takahara, Akiko Kusano, Makio Shibano, Genjiro Kusano, Kenzo Koizumi, Ryuji Suzuki, Hye-Sook Kim, Yusuke Wataya

    Biological and Pharmaceutical Bulletin21 ( 8 ) 823 - 828   1998年

     詳細を見る

    記述言語:英語   出版者・発行元:Pharmaceutical Society of Japan  

    The in vitro antimalarial activity against human malaria parasite (Plasmodium falciparum, FCR-3 strain) was examined using 59 triterpenoids obtained during studies on the triterpenic constituents of Cimicifuga spp. The 50% effective concentration values (EC50) of 25 active triterpenoids were 1.0-3.0 μM, and 19 of the compounds had a common 16, 23 : 23, 26 : 24, 25-triepoxy group in the side-chain moieties. Among the active triterpenoids, 9 also showed significant inhibition of nucleoside transport in mouse splenocytes. A relationship between the antimalarial activity and the inhibition of nucleoside transport involving these triterpenoids is discussed.

    DOI: 10.1248/bpb.21.823

    Scopus

    PubMed

    researchmap

  • Antimalarial activity and nucleoside transport inhibitory activity of the triterpenic constituents of Cimicifuga spp.

    Masayuki Takahara, Akiko Kusano, Makio Shibano, Genjiro Kusano, Kenzo Koizumi, Ryuji Suzuki, Hye-Sook Kim, Yusuke Wataya

    Biological and Pharmaceutical Bulletin21 ( 8 ) 823 - 828   1998年

     詳細を見る

    記述言語:英語   出版者・発行元:Pharmaceutical Society of Japan  

    The in vitro antimalarial activity against human malaria parasite (Plasmodium falciparum, FCR-3 strain) was examined using 59 triterpenoids obtained during studies on the triterpenic constituents of Cimicifuga spp. The 50% effective concentration values (EC50) of 25 active triterpenoids were 1.0-3.0 μM, and 19 of the compounds had a common 16, 23 : 23, 26 : 24, 25-triepoxy group in the side-chain moieties. Among the active triterpenoids, 9 also showed significant inhibition of nucleoside transport in mouse splenocytes. A relationship between the antimalarial activity and the inhibition of nucleoside transport involving these triterpenoids is discussed.

    DOI: 10.1248/bpb.21.823

    Scopus

    PubMed

    researchmap

  • Antimalarial activity and structure-activity relationships of protoberberine alkaloids

    Kinuko Iwasa, Hye-Sook Kim, Yusuke Wataya, Dong-Ung Lee

    European Journal of Medicinal Chemistry33 ( 1 ) 65 - 69   1998年

     詳細を見る

    記述言語:英語   出版者・発行元:Elsevier Masson SAS  

    The thirty-nine protoberberine derivatives including berberine 1 and palmatine 2 were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the quaternary nitrogen atom, the nature and the size of the substituents at the C-13 position, and the type of O-alkyl substituents on rings A and D. The activity of the quaternary protoberberinium salts with an aromatic ring C such as berberine was higher than that of the quaternary salts such as the N-metho salts or the N-oxides of tetrahydro and dihydro derivatives as well as tertiary tetrahydroprotoberberines. Of the 13-alkyl derivatives of 1 and 2, the activity did not always increase as the length of the aliphatic chain rose in the order methyl, ethyl, propyl, butyl, and hexyl group. 13- Butylberberine (1Bu) and 13-propylpalmatine (2Pr) were the most active compounds among the 13-alkylberberines and 13-alkylpalmatines, respectively. 13-Hydroxyberberine 3 possessed the same level of activity as 1. Of 1 and 2 with different substituents types on Ring A, the activity of 1 was significantly higher than that of 2. Among berberrubines 4 and 5 and their C- 9-O-alkyl derivatives 6 and 7, the activity of 9-O-ethylberberrubine 6 was the highest. Of the potent protoberberinium salts, the activity decreased in the order: 1, 3 &gt
    2Pr &gt
    6 &gt
    1Bu. A positive effect on the activity might be exerted by the introduction of a more hydrophilic function into the C-13 position of the protoberberinium salts.

    DOI: 10.1016/S0223-5234(99)80077-4

    Scopus

    researchmap

  • Antimalarial activity and structure-activity relationships of protoberberine alkaloids

    Kinuko Iwasa, Hye-Sook Kim, Yusuke Wataya, Dong-Ung Lee

    European Journal of Medicinal Chemistry33 ( 1 ) 65 - 69   1998年

     詳細を見る

    記述言語:英語   出版者・発行元:Elsevier Masson SAS  

    The thirty-nine protoberberine derivatives including berberine 1 and palmatine 2 were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the quaternary nitrogen atom, the nature and the size of the substituents at the C-13 position, and the type of O-alkyl substituents on rings A and D. The activity of the quaternary protoberberinium salts with an aromatic ring C such as berberine was higher than that of the quaternary salts such as the N-metho salts or the N-oxides of tetrahydro and dihydro derivatives as well as tertiary tetrahydroprotoberberines. Of the 13-alkyl derivatives of 1 and 2, the activity did not always increase as the length of the aliphatic chain rose in the order methyl, ethyl, propyl, butyl, and hexyl group. 13- Butylberberine (1Bu) and 13-propylpalmatine (2Pr) were the most active compounds among the 13-alkylberberines and 13-alkylpalmatines, respectively. 13-Hydroxyberberine 3 possessed the same level of activity as 1. Of 1 and 2 with different substituents types on Ring A, the activity of 1 was significantly higher than that of 2. Among berberrubines 4 and 5 and their C- 9-O-alkyl derivatives 6 and 7, the activity of 9-O-ethylberberrubine 6 was the highest. Of the potent protoberberinium salts, the activity decreased in the order: 1, 3 &gt
    2Pr &gt
    6 &gt
    1Bu. A positive effect on the activity might be exerted by the introduction of a more hydrophilic function into the C-13 position of the protoberberinium salts.

    DOI: 10.1016/S0223-5234(99)80077-4

    Scopus

    researchmap

  • 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 & NUCLEOTIDES15 ( 1-3 ) 719 - 731   1996年

     詳細を見る

    記述言語:英語   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.

    Web of Science

    researchmap

  • 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 & NUCLEOTIDES15 ( 1-3 ) 719 - 731   1996年

     詳細を見る

    記述言語:英語   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.

    Web of Science

    researchmap

▼全件表示

講演・口頭発表等

  • 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 

     詳細を見る

  • 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 

     詳細を見る

  • 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 

     詳細を見る

  • 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 

     詳細を見る

  • 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 

     詳細を見る

  • 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 

     詳細を見る

  • 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 

     詳細を見る

  • New antimalarial drug development research -antimalarial synthetic endoperoxides-

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

     詳細を見る

  • 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 

     詳細を見る

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

 

担当授業科目

  • 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