Anti-AIDS agents 69. Moronic acid and other triterpene derivatives as novel potent anti-HIV agents.

Published

Journal Article

In a continuing structure-activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20, and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compounds 19 and 20 were also evaluated against HIV-1 NL4-3 and drug resistant strains in the MT-4 cell line. Compounds 19 and 20 showed better antiviral profiles than the betulinic acid analogue 8 (PA-457), which has successfully completed a Phase IIa clinical trial. Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 microM against NL4-3, 0.021 microM against PI-R (a multiple protease inhibitor resistant strain), and 0.13 microM against FHR-2 (an HIV strain resistant to 8). Promising compound 20 has become a new lead for modification, and further development of 20-related compounds as clinical trial candidates is warranted.

Full Text

Duke Authors

Cited Authors

  • Yu, D; Sakurai, Y; Chen, C-H; Chang, F-R; Huang, L; Kashiwada, Y; Lee, K-H

Published Date

  • September 2006

Published In

Volume / Issue

  • 49 / 18

Start / End Page

  • 5462 - 5469

PubMed ID

  • 16942019

Pubmed Central ID

  • 16942019

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

International Standard Serial Number (ISSN)

  • 0022-2623

Digital Object Identifier (DOI)

  • 10.1021/jm0601912

Language

  • eng