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

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.

SUBMITTER: Xiong J

PROVIDER: S-EPMC3016297 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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

Xiong Juan J Kashiwada Yoshiki Y Chen Chin-Ho CH Qian Keduo K Morris-Natschke Susan L SL Lee Kuo-Hsiung KH Takaishi Yoshihisa Y

Bioorganic & medicinal chemistry 20100707 17

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 ...[more]

PMID: 20673723

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