Conjugates of betulin derivatives with AZT as potent anti-HIV agents

Fourteen novel conjugates of 3,28-di-O-acylbetulins with AZT were prepared as anti-HIV agents, based on our previously reported potent anti-HIV triterpene leads, including 3-O-acyl and 3,28-di-O-acylbetulins. Nine of the conjugates (49–53, 55, 56, 59, and 60) exhibited potent anti-HIV activity at the submicromolar level, with EC50 values ranging from 0.040 to 0.098 μM in HIV-1NL4-3 infected MT-4 cells. These compounds were equipotent or more potent than 3-O-(3′,3′-dimethylsuccinyl)betulinic acid (2), which is currently in Phase IIb anti-AIDS clinical trial.

Fourteen novel conjugates of 3,28-di-O-acyl-betulins with AZT were prepared as anti-HIV agents. Among them, nine conjugates were equipotent or more potent than bevirimat, which is currently in Phase IIb anti-AIDS clinical trial.Figure optionsDownload as PowerPoint slide