2. Academic Validation
  3. New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1

New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1

  • J Med Chem. 2013 Mar 14;56(5):2029-37. doi: 10.1021/jm3016969.
Zhao Dang 1,  Phong Ho,  Lei Zhu,  Keduo Qian,  Kuo-Hsiung Lee,  Li Huang,  Chin-Ho Chen
Affiliations

Affiliation

  • 1 Surgical Science, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, United States.
PMID: 23379607 DOI: 10.1021/jm3016969
Abstract

Bevirimat (1, BVM) is an anti-HIV agent that blocks HIV-1 replication by interfering with HIV-1 Gag-SP1 processing at a late stage of viral maturation. However, clinical trials of 1 have revealed a high baseline drug resistance that is attributed to naturally occurring polymorphisms in HIV-1 Gag. To overcome the drug resistance, 28 new derivatives of 1 were synthesized and tested against compound 1-resistant (BVM-R) HIV-1 variants. Among them, compound 6 exhibited much improved activity against several HIV-1 strains carrying BVM-R polymorphisms. Compound 6 was at least 20-fold more potent than 1 against the replication of NL4-3/V370A, which carries the most prevalent clinical BVM-R polymorphism in HIV-1 Gag-SP1. Thus, compound 6 merits further development as a potential anti-AIDS clinical trial candidate.

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