| Project/Area Number |
11307052
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Kitasato University (2001-2002)
Kitasato Institute (1999-2000) |
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Principal Investigator |
OMURA Satoshi Kitasato University, Kitasato Institute for Life Sciences, Professor, 北里生命科学研究所, 教授 (90050426)
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| Co-Investigator(Kenkyū-buntansha) |
TOMODA Hiroshi Kitasato University, Kitasato Institute for Life Sciences, Professor, 北里生命科学研究所, 教授 (70164043)
OTOGURO Kazuhiko The Kitasato Institute, Research Center for Tropical Diseases, Director, 基礎研究所・熱帯病研究センター, センター長 (80118794)
YAMADA Haruki Kitasato University, Kitasato Institute for Life Sciences, Professor, 北里生命科学研究所, 教授 (60096691)
UI Hideaki Kitasato University, School of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (90290957)
KIYOHARA Hiroaki Kitasato University, Kitasato Institute for Life Sciences, Associate Professor, 北里生命科学研究所, 助教授 (70161601)
塩見 和朗 社団法人 北里研究所, 生物機能研究所, 室長 (40235502)
林 正彦 社団法人 北里研究所, 基礎研究所, 室長 (20164965)
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| Project Period (FY) |
1999 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥40,260,000 (Direct Cost: ¥36,600,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2002: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2001: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2000: ¥10,900,000 (Direct Cost: ¥10,900,000)
Fiscal Year 1999: ¥13,500,000 (Direct Cost: ¥13,500,000)
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| Keywords | antimalarial drugs / chemistry of natural products / microbial resource / plant resource / purification of active compounds / elucidation of structure / marine products / synthesis of derivatives |
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| Research Abstract |
We had researched to discover new type of the antimalarial drugs from the natural products. During the research period of 4 years, 12, 832 samples as the natural products were supplied to the Kitasato screening center for in vitro antimalarial screening. As a result, we selected the candidate materials as 18 natural products that had selective and potent antimalarial activities, which must be examined further isolation and purification of active compounds from those materials. In the course of the research from the microbial metabolites, we found that the five known antibiotics (X-206, K-41, polyketomycin, borrelidin and leucinostatin A) produced by actinomycete strains K99-0413, KP-4050, K99-5147, KP-4093 (later, OM-0060 was selected as highly productive strain) and a fungal strain FKI-0266, respectively, had potent and selective antimalarial activities in vitro. Further, we found that takaokamycin (identified with hormomycin) and octacyclomycin, own compounds in the antibiotic library of our institute, had potent activity in vitro. Furthermore, the in vivo antimalarial activities of X-206, K-41 and borrelidin exhibited more potent activities than those of the existed antimalarial drugs as artemether, artesunate and chloroquine. Especially, K-41 and borrelidin has the possibility of the lead compounds as the new type of the antimalarial drugs, further detail studies of K-41 and borrelidin are in progress. In the course of the research from the plant resources, we found that two known biflavonoids as sikokianins B and C were isolated from the root of Wikstroemia indica, had moderate antimaralial activities in vitro. There are the first reports to show antimalarial activities of the above compounds. Now, we are ongoing to measure the antimalarial activities of other natural compounds as marine products and synthetic compounds derived from the natural products, and also ongoing to isolate active substances from the other natural products.
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