2. Academic Validation
  3. Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors

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

  • ACS Med Chem Lett. 2016 Jan 9;7(3):240-4. doi: 10.1021/acsmedchemlett.5b00339.
Zhao Dang 1,  Lei Zhu 1,  Weihong Lai 1,  Hal Bogerd 2,  Kuo-Hsiung Lee 3,  Li Huang 1,  Chin-Ho Chen 1
Affiliations

Affiliations

  • 1 Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
  • 2 Department of Molecular Genetics and Microbiology, Duke University Medical Center , Durham, North Carolina 27710, United States.
  • 3 Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States; Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan.
PMID: 26985308 DOI: 10.1021/acsmedchemlett.5b00339
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.

Keywords

HIV-1; aloperine; entry inhibitor.

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