DNA polymerase beta inhibitors from Baeckea gunniana

Crude plant extracts were surveyed for their ability to inhibit DNA polymer ase beta. A methyl ethyl ketone extract prepared from Baeckea gunniana was identified as a potent inhibitor of the enzyme. Bioassay-guided fractionati on of the extract, using an assay to monitor the inhibitory potential of in dividual fractions toward DNA polymerase beta, led to the isolation of four active ursane and oleanane triterpenoids (1-4). Inhibitory principle 1 is a new natural product, and 2 is a novel compound. Their structures were est ablished as 3 beta-hydroxyurs-12,19(29)-dien-28-oic acid (1) and 3 beta-hyd roxyurs-18,20(30)-dien-28-oic acid (2) by spectroscopic analysis and by com parison with the data for the structurally related compound ursolic acid (4 ). Also isolated as a DNA polymerase beta inhibitor was oleanolic acid (3). Compounds 1-4 had IC50 values of 5.3-8.5 mu M as inhibitors of polymerase beta in the presence of bovine serum albumin (BSA) and 2.5-4.8 mu M in the absence of BSA.