Development of anti-HIV agents with dual mechanisms of actions based on triterpenoids as drug discovery templates
| Project/Area Number |
15K07998
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Natural medicines
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KASHIWADA Yoshiki 徳島大学, 大学院医歯薬学研究部(薬学系), 教授 (30169429)
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| Co-Investigator(Kenkyū-buntansha) |
田中 直伸 徳島大学, 大学院社会産業理工学研究部(生物資源産業学域), 准教授 (40455598)
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| Research Collaborator |
LEE KUO-HSIUNG ノースカロライナ大学チャペルヒル校, エシェルマン薬学部, 教授
Qian Keduo ノースカロライナ大学チャペルヒル校, エシェルマン薬学部, 助教
CHEN CHIN-HO デューク大学, 医学部, 教授
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | HIV / 薬剤耐性 / トリテルペン / ベツリン酸 / 抗HIV薬 |
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| Outline of Final Research Achievements |
Based on our finding of a first-in-class drug candidate as a viral maturation inhibitor, bevirimat [3-O-(3',3'-dimethylsuccinyl)-betulinic acid], and potent anti-HIV active 3-O-acyl-(dihidro)betulin derivatives (e.g. 3-O-glutarydihydrobetulin and 3,28-di-O-dimethylsuccinylbetulin), a series of conjugates of 3,28-di-O-acylbetulin derivatives and HIV-reverse transcriptase inhibitor, AZT, with a linker moiety containing glycine, were prepared and evaluated their anti-HIV activity. Several derivatives showed more potent anti-HIV activity than bevirimat. In addition, preliminary study for preparing conjugate of betulinic acid derivative and AZT, where 5'-position of AZT is not involved, resulted in the finding of quite potential anti-HIV agents. Further study is in progress.
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Report
(4 results)
Research Products
(5 results)
