| Project/Area Number |
16390031
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
KIM Hyesook Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (70314664)
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| Co-Investigator(Kenkyū-buntansha) |
WATAYA Yusuke Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (90127598)
KIMURA Mikio National Institute of infectious Diseases, Infectious Disease Surveillance Center, Leader, 感染症情報センター, 室長 (90114462)
KAWAI Satoru Dokkyo Medicinal University, School of medicine, Associate Professor, 医学部, 助教授 (70275733)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2005: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2004: ¥10,800,000 (Direct Cost: ¥10,800,000)
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| Keywords | malaria / endoperoxides / drug-resistant / antimalarials / johzan alkaloid / mechanism analysis / 天然生薬抗マラリア資源 / 薬剤耐性メカニズム |
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| Research Abstract |
Our research objective is development of new antiamalarial drug against drug-resistant Plasmodium falciparum and our study is advanced for the purpose of contributing to the malaria suppression. For the antimalarial action mechanism of our research, we using endopeoxides, which is the organic compound and these chemical compounds with the selection of the high antimalarial action, and other compound, johzan alkaloid analogs, which are natural, product derived from Dichroa febrifuga.
The research result of this study is shown at the following.
1.Mechanism of endoperoxide antimalarials was comprehensively analyzed. Base on the 2 dimensional electrophoretic conditions for separation of parasite proteins, it came out in comparison with the pattern of the protein with the difference of control- and endoperoxide treated protein pattern. Different protein spots were cut and analyzed with MALDI- TOF/MS, and the protein was identified. As a result, several parasite proteins were detected, such as cytosketal protein, nutrient related protein and client protein of parasite. Furthermore, drug target of endoperoxide in malaria parasite was detected.
2.Endoperoxide resistant P.falciparum strain (parasite grow under the 1 × 10^<-7>M of drug pressure) were acquired in vitro culture using drug pressure of endoperoxide and cloning technique.
3.One of ten analogs of Johzan alkaloids has high antiamlarial activity with low cytotoxicity.
4.Transcriptome analysis for the dissolving the mefloquine-resistant mechanism of P.falciparum was done. As a results, gene expression level of pfmdr-1 and pfmrp, were not changed. Combination treatment of anti-tuberculosis and endoperoxide shows reverse effect against mefloquine-resistant P.falciparum.
Base on the upper results, we would like to decide the target molecule of malaria parasite for endoperoxide
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