Anti-AIDS agents 38. Anti-HIV activity of 3-O-acyl ursolic acid derivatives.
Based on our previous finding that 3-O-acyl-betulinic and -oleanolic acids, especially the 3-O-(3',3'-dimethyl)-succinyl derivatives (2 and 4), demonstrated potent anti-HIV activity [EC(50) < 0.00035 and 0.00086 microM; therapeutic index (TI) > 20 000 and 22 326, respectively], several 3-O-acyl-ursolic acids were prepared and evaluated for anti-HIV activity. Ursolic acid (6) was equipotent (EC(50) 4.4 microM) with oleanolic acid (EC(50) 3.7 microM), although it was slightly toxic (IC(50) 14.3 microM, TI 3.3). 3-O-Diglycoryl-ursolic acid (10) demonstrated relatively potent anti-HIV activity with an EC(50) of 0. 31 microM and a TI of 155.5. In contrast, 3-O-(3', 3'-dimethylsuccinyl)-ursolic acid (8), which is analogous to the extremely potent anti-HIV betulinic acid and oleanolic acid derivatives 2 and 4, displayed only weak anti-HIV activity (EC(50) 2.1 microM, TI 23.6).
Kashiwada
Y
Y
Niigata College of Pharmacy, Kamishin'ei-cho, Niigata 950-2081, Japan, Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Nagao
T
T
Hashimoto
A
A
Ikeshiro
Y
Y
Okabe
H
H
Cosentino
L M
LM
Lee
K H
KH
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D000097245:Ursolic Acid
D019380:Anti-HIV Agents; D014315:Triterpenes; D000097245:Ursolic Acid