2. Academic Validation
  3. Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors

Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors

  • ACS Med Chem Lett. 2017 Oct 9;8(11):1199-1203. doi: 10.1021/acsmedchemlett.7b00376.
Zhao Dang 1,  Hua Xie 2,  Lei Zhu 1,  Qingye Zhang 3 4,  Zhijun Li 3,  Li Huang 1,  Chin-Ho Chen 1
Affiliations

Affiliations

  • 1 Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, United States.
  • 2 School of Dentistry, Meharry Medical College, Nashville, Tennessee 37208, United States.
  • 3 Department of Chemistry & Biochemistry, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania 19104, United States.
  • 4 College of Informatics, Huazhong Agricultural University, Wuhan, Hubei 430070, P. R. China.
PMID: 29152054 DOI: 10.1021/acsmedchemlett.7b00376
Abstract

As a step toward developing novel anti-HIV agents, we have identified a class of quinolizidines, including aloperine, that inhibit HIV at 1-5 μM by blocking viral entry. In this study, we have optimized the structure of aloperine and derived compounds with markedly improved activity. Our structural optimization has yielded an aloperine derivative 19 with approximately a 15-fold increase in anti-HIV-1 activity. Our mechanism of action study reveals that compound 19 does not inhibit binding of HIV-1 to receptors but arrests the virus from fusion with the membrane. Binding of the compound to HIV-1gp120 might be responsible for its anti-HIV-1 entry activity.

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