Synthesis and anti-HIV activity of bi-functional betulinic acid derivatives.
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.
Duke Scholars
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- Triterpenes
- Pentacyclic Triterpenes
- Molecular Conformation
- Microbial Sensitivity Tests
- Medicinal & Biomolecular Chemistry
- HIV-1
- Chlorocebus aethiops
- Cell Fusion
- COS Cells
- Betulinic Acid
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Triterpenes
- Pentacyclic Triterpenes
- Molecular Conformation
- Microbial Sensitivity Tests
- Medicinal & Biomolecular Chemistry
- HIV-1
- Chlorocebus aethiops
- Cell Fusion
- COS Cells
- Betulinic Acid