Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors

被引：66

作者：

Dang, Zhao ^{[1
]}

Zhu, Lei ^{[1
]}

Lai, Weihong ^{[1
]}

Bogerd, Hal ^{[2
]}

Lee, Kuo-Hsiung ^{[3
,4
]}

Huang, Li ^{[1
]}

Chen, Chin-Ho ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Dept Surg, Surg Sci, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA

[3] Univ N Carolina, Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA

[4] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2016年 / 7卷 / 03期

关键词：

HIV-1; entry inhibitor; aloperine; IMMUNODEFICIENCY-VIRUS TYPE-1; BETULINIC ACID-DERIVATIVES; ATTACHMENT INHIBITOR; ANTIRETROVIRAL THERAPY; PRODRUG BMS-663068; GP120; RESISTANT; INFECTION; ENVELOPE; IDENTIFICATION;

D O I：

10.1021/acsmedchemlett.5b00339

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A quinolizidine-type alkaloid aloperine was found to inhibit HIV-1 infection by blocking HIV-1 entry. Aloperine inhibited HIV-1 envelope-mediated cell cell fusion at low micromolar concentrations. To further improve the antiviral potency, more than 30 aloperine derivatives with a variety of N12-substitutions were synthesized. Among them, 12d with an N-(1-butyl)-4-trifluorome-thoxy-benzamide side chain showed the most potent anti-HIV-1 activity with EC50 at 0.69 mu M. Aloperine derivatives inhibited both X4 and R5 HIV-1 Env-mediated cell cell fusions. In addition, both BMS-806, a compound representing a class of HIV-1 gp120-targeting small molecules in clinical trials, and resistant and sensitive HIV-1 Env-mediated cell cell fusions were equally sensitive to aloperine derivatives. These results suggest that aloperine and its derivatives are a new class of anti-HIV-1 entry inhibitors.

引用

页码：240 / 244

页数：5

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