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Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors.

ABSTRACT: As a step toward developing novel anti-HIV agents, we have identified a class of quinolizidines, including aloperine, that inhibit HIV at 1-5 ?M by blocking viral entry. In this study, we have optimized the structure of aloperine and derived compounds with markedly improved activity. Our structural optimization has yielded an aloperine derivative 19 with approximately a 15-fold increase in anti-HIV-1 activity. Our mechanism of action study reveals that compound 19 does not inhibit binding of HIV-1 to receptors but arrests the virus from fusion with the membrane. Binding of the compound to HIV-1gp120 might be responsible for its anti-HIV-1 entry activity.

SUBMITTER: Dang Z

PROVIDER: S-EPMC5683702 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors.

Dang Zhao Z Xie Hua H Zhu Lei L Zhang Qingye Q Li Zhijun Z Huang Li L Chen Chin-Ho CH

ACS medicinal chemistry letters 20171009 11

As a step toward developing novel anti-HIV agents, we have identified a class of quinolizidines, including aloperine, that inhibit HIV at 1-5 μM by blocking viral entry. In this study, we have optimized the structure of aloperine and derived compounds with markedly improved activity. Our structural optimization has yielded an aloperine derivative <b>19</b> with approximately a 15-fold increase in anti-HIV-1 activity. Our mechanism of action study reveals that compound <b>19</b> does not inhibit ...[more]

PMID: 29152054

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