LUPANE DERIVATIVES FROM LOPHOPETALUM-WALLICHII WITH FARNESYL-PROTEIN TRANSFERASE INHIBITORY ACTIVITY

Chloroform-soluble extracts of the stems and of the mixed stems and st em bark of Lophopetalum wallichii were found to be inhibitory in a far nesyl protein transferase (FPTase) bioassay system. During the course of activity-guided fractionation, the known lupane-type triterpenes, o chraceolide A (1), ochracelide B (2), betulin, and lupeol and the new lupane lactone, dihydro ochraceolide A (4), were isolated. The stereoc hemistry of the epoxide isomers [2, and new semisynthetic derivative, 20-epi-ochraceolide B (3)] from 1. The structure of 4 was established by reduction of 1 with sodium borohydride. Compounds 1 and 2 exhibited significant inhibitory activity in the FPTase assay (IC50 values of 1 .0 and 0.7 mu g/mL, respectively). Lupeol was found to be weakly activ e (IC50 65.0 mu g/mL) in this test system, whereas no significant inhi bition was detected fro betulin or compounds 3 or 4. When evaluated ag ainst a panel of human cancer cells in culture, compounds 1 and 4 were modestly cytotoxic. Compounds 2 and 3 were not active in the panel.