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

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.