Incorporation of Privileged Structures into Bevirimat Can Improve Activity against Wild-Type and Bevirimat-Resistant HIV-1.

Published

Journal Article

Two "privileged fragments", caffeic acid and piperazine, were integrated into bevirimat producing new derivatives with improved activity against HIV-1/NL4-3 and NL4-3/V370A carrying the most prevalent bevirimat-resistant polymorphism. The activity of one of these, 18c, was increased by 3-fold against NL4-3 and 51-fold against NL4-3/V370A. Moreover, 18c is a maturation inhibitor with improved metabolic stability. Our study suggested that integration of privileged motifs into promising natural product skeletons is an effective strategy for discovering potent derivatives.

Full Text

Duke Authors

Cited Authors

  • Zhao, Y; Gu, Q; Morris-Natschke, SL; Chen, C-H; Lee, K-H

Published Date

  • October 2016

Published In

Volume / Issue

  • 59 / 19

Start / End Page

  • 9262 - 9268

PubMed ID

  • 27676157

Pubmed Central ID

  • 27676157

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

International Standard Serial Number (ISSN)

  • 0022-2623

Digital Object Identifier (DOI)

  • 10.1021/acs.jmedchem.6b00461

Language

  • eng