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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Dang, Z; Ho, P; Zhu, L; Qian, K; Lee, K-H; Huang, L; Chen, C-H

Published Date

  • March 14, 2013

Published In

Volume / Issue

  • 56 / 5

Start / End Page

  • 2029 - 2037

PubMed ID

  • 23379607

Pubmed Central ID

  • PMC3600082

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

Digital Object Identifier (DOI)

  • 10.1021/jm3016969


  • eng

Conference Location

  • United States