Conjugates of betulin derivatives with AZT as potent anti-HIV agents.
Bioorganic & medicinal chemistry 2010 Jul 7; In press
Xiong J, Kashiwada Y, Chen C CH, Qian K, Morris-Natschke S SL, Lee K KH, Takaishi Y
Graduate School of Pharmaceutical Sciences, University of Tokushima, Tokushima 770-8505, Japan.
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 EC(50) values ranging from 0.040 to 0.098muM in HIV-1(NL4-3) 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.