Anti-AIDS Agents 38. Anti-HIV Activity of 3-O-Acyl Ursolic Acid Derivatives

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Abstract
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 [EC50 < 0.00035 and 0.00086 μM; 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 (EC50 4.4 μM) with oleanolic acid (EC50 3.7 μM), although it was slightly toxic (IC50 14.3 μM, TI 3.3). 3-O-Diglycoryl-ursolic acid (10) demonstrated relatively potent anti-HIV activity with an EC50 of 0.31 μM 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 (EC50 2.1 μM, TI 23.6).