| Project/Area Number |
12557197
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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 | 展開研究 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
OSHIMA Yoshiteru Tohoku University, Graduate School of Pharm. Sci., Professor, 大学院・薬学研究科, 教授 (00111302)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAYA Yoshiaki Meiji Univ., Faculty of Pharm. Sci., Associate Professor, 薬学部, 助教授 (80301034)
HATAKEYAMA Susumu Nagasaki Univ., Faculty of Pharm. Sci., Professor, 薬学部, 教授 (20143000)
WATAYA Yusuke Okayama Univ., Faculty of Pharm. Sci., Professor, 大学院・自然科学研究科, 教授 (90127598)
KIKUCHI Haruhisa Tohoku University, Graduate School of Pharm. Sci., Instructor, 大学院・薬学研究科, 助手 (90302166)
KURATA Shoichiro Tohoku University, Graduate School of Pharm. Sci., Associate Professor, 大学院・薬学研究科, 助教授 (90221944)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2001: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2000: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Dichroa febrifuga / Alkaloid / Febrifugine / Antimalarial activity / 甘松香 / テルペノイド |
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| Research Abstract |
Although febrifugine and isofebrifugine, alkaloids isolated from Dichroa febrifuga roots, show powerful antimalarial activities against Plasmodium falciparum, their strong side effects such as emetic effect precluded their clinical use in malaria. However, their antimalarial potency makes them attractive substances as leads for developing new types of chemotherapeutic antimalarial drugs. We have thus evaluated the in vitro antimalarial activity of analogues of febrifugine and isofebrifugine. The activities of analogues derived from Df-1 and Df-2, condensation products of febrifugine and isofebrifugine with acetone, respectively, were also obtained. The oxidation and reduction derivatives of febrifugine were found to exhibit potential antimalarial activities with high selectivities against P. falciparum in vitro. Additionally, the Dess-Martin oxidation product of Df-1 was found to be strongly active with high selectivity against P. falciparum. A structure-activity relationship study demonstrates the essential role played by the 4-quinazolinone ring in the appearance of activity, and that the presence of a 1"-amino group and C-2', C-3" 0-functionalities are crucial in the activity of febrifugine.
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