Synthesis and anti-HIV activity of bi-functional betulinic acid derivatives.
Journal Article (Journal Article)
Betulinic acid (BA) derivatives with a side chain at C-3 can inhibit HIV-1 maturation. On the other hand, BA derivatives with a side chain at C-28 can block HIV-1 entry. In order to combine the anti-maturation and anti-entry activities in a single molecule, new bi-functional BA derivatives containing side chains at C-3 and C-28 have been synthesized. The most potent compound ([[N-[3beta-O-(3',3'-dimethylsuccinyl)-lup-20(29)-en-28-oyl]-7-aminoheptyl]-carbamoyl]methane) inhibited HIV-1 at an EC50 of 0.0026 microM and was at least 20 times more potent than either the anti-maturation lead compound DSB or the anti-entry lead compound IC9564. This bi-functional BA derivative was active against both HIV entry and maturation. These results suggest that bi-functional BA derivatives with dual mechanisms of action have the potential to become clinically useful for AIDS therapy.
Full Text
Duke Authors
Cited Authors
- Huang, L; Ho, P; Lee, K-H; Chen, C-H
Published Date
- April 1, 2006
Published In
Volume / Issue
- 14 / 7
Start / End Page
- 2279 - 2289
PubMed ID
- 16314103
International Standard Serial Number (ISSN)
- 0968-0896
Digital Object Identifier (DOI)
- 10.1016/j.bmc.2005.11.016
Language
- eng
Conference Location
- England