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

Abstract

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-trifluoromethoxy-benzamide side chain showed the most potent anti-HIV-1 activity with EC50 at 0.69 μM. 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.

• Authors: Zhao Dang, Lei Zhu, Weihong Lai, Hal Bogerd, Kuo-Hsiung Lee, Li Huang, Chin-Ho Chen
• Journal: ACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 7 Issue 3 Pg. 240-4 (Mar 10 2016) ISSN: 1948-5875 [Print] United States
• PMID: 26985308 (Publication Type: Journal Article)