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

Authors :: Xiong J
Kashiwada Y
Chen CH
Qian K
Morris-Natschke SL
Lee KH
Takaishi Y
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2010 Sep 01; Vol. 18 (17), pp. 6451-69. Date of Electronic Publication: 2010 Jul 07.
Publication Year :: 2010
Abstract: 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.<br /> (Copyright 2010 Elsevier Ltd. All rights reserved.)