Anti-AIDS agents. Part 61: Anti-HIV activity of new podophyllotoxin derivatives

Abstract

A series of novel podophyllotoxin derivatives containing structural modifications at C-4 ( 7– 14), C-4′ ( 16– 17), and the methylenedioxy A-ring ( 23– 28) was synthesized and tested for inhibition of HIV replication. Four of these compounds ( 25– 28) were previously reported to show EC 50 values of <0.001 μg/mL and therapeutic index (TI) values >120. Three of the newly tested compounds ( 8, 12, and 20) showed good activity with EC 50 values of 0.012, <0.001, and 0.389 μg/mL and TI values of 19.1, >16, and 19.4, respectively. A comparison of the anti-HIV activity of these derivatives suggested that an opened A-ring with 6,7-dimethoxy substitution and a 4′-demethylated E ring enhanced anti-HIV activity.