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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Dang, Z; Zhu, L; Lai, W; Bogerd, H; Lee, K-H; Huang, L; Chen, C-H

Published Date

  • March 10, 2016

Published In

Volume / Issue

  • 7 / 3

Start / End Page

  • 240 - 244

PubMed ID

  • 26985308

Pubmed Central ID

  • PMC4789664

International Standard Serial Number (ISSN)

  • 1948-5875

Digital Object Identifier (DOI)

  • 10.1021/acsmedchemlett.5b00339


  • eng

Conference Location

  • United States