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 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.
Xiong
Juan
J
Graduate School of Pharmaceutical Sciences, University of Tokushima, Tokushima 770-8505, Japan.
Kashiwada
Yoshiki
Y
Chen
Chin-Ho
CH
Qian
Keduo
K
Morris-Natschke
Susan L
SL
Lee
Kuo-Hsiung
KH
Takaishi
Yoshihisa
Y
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000094062:Betulinic Acid
D019380:Anti-HIV Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D015215:Zidovudine; C002503:betulin; D000094062:Betulinic Acid