ANTI-AIDS AGENTS - 30 - ANTI-HIV ACTIVITY OF OLEANOLIC ACID, POMOLIC ACID, AND STRUCTURALLY RELATED TRITERPENOIDS

Oleanolic acid (1) was identified as an anti-HIV principle from severa l plants, including Rosa woodsii (leaves), Prosopis glandulosa (leaves and twigs), Phoradendron juniperinum (whole plant), Syzygium claviflo rum (leaves), Hyptis capitata (whole plant), and Ternstromia gymnanthe ra (aerial part). It inhibited HIV-1 replication in acutely infected H 9 cells with an EC50 value of 1.7 mu g/mL, and inhibited H9 cell growt h with an IC50 value of 21.8 mu g/mL [therapeutic index (T. I.) 12.8]. Pomolic acid, isolated from R. woodsii and H. capitata, was also iden tified as an anti-HIV agent (EC50 1.4 mu g/mL, T. I. 16.6). Although u rsolic acid did show anti-HIV activity (EC50 2.0 mu g/mL), it was slig htly toxic (IC50 6.5 mu g/mL, T. I. 3.3). A new triterpene (11) was al so isolated from the CHCl3-soluble fraction of R. woodsii, though it s howed no anti-HIV activity. The structure of 11 was determined to be 1 beta-hydroxy-2-oxopomolic acid by spectral examination. Based on thes e results, we examined the anti-HIV activity of oleanolic acid- or pom olic acid-related triterpenes isolated from several plants. In additio n, we previously demonstrated that derivatives of betulinic acid, isol ated from the leaves of S. claviflorum as an anti-HIV principle, exhib ited extremely potent anti-HIV activity. Accordingly, we prepared deri vatives of oleanolic acid and evaluated their anti-HIV activity. Among the oleanolic acid derivatives, 18 demonstrated most potent anti-HIV activity, with an EC50 value of 0.0005 mu g/mL and a T. I. value of 22 400.