title: 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.affiliation: Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Dang
authors.affiliation: Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Weihong
authors.initials: W
authors.lastname: Lai
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Hal
authors.initials: H
authors.lastname: Bogerd
authors.affiliation: 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.
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Surgical Science, Department of Surgery, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Chin-Ho
authors.initials: CH
authors.lastname: Chen
keywords: HIV-1; aloperine; entry inhibitor