Development of anti-HIV agents with dual mechanisms of actions based on triterpenoids as drug discovery templates

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07998
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: The University of Tokushima
• Principal Investigator: KASHIWADA Yoshiki 徳島大学, 大学院医歯薬学研究部(薬学系), 教授 (30169429)
• 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)
• 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
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: HIV / 薬剤耐性 / トリテルペン / ベツリン酸

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.

Free Research Field

Natural Product Chemistry