DNA polymerase β inhibitors from Baeckea gunniana

Crude plant extracts were surveyed for their ability to inhibit DNA polymerase β. A methyl ethyl ketone extract prepared from Baeckea gunniana was identified as a potent inhibitor of the enzyme. Bioassay-guided fractionation of the extract, using an assay to monitor the inhibitory potential of individual fractions toward DNA polymerase β, 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 established as 3β-hydroxyurs-12,19(29)-dien-28- oic acid (1) and 3β-hydroxyurs-18,20(30)-dien-28-oic acid (2) by spectroscopic analysis and by comparison with the data for the structurally related compound ursolic acid (4). Also isolated as a DNA polymerase β inhibitor was oleanolic acid (3). Compounds 1-4 had IC₅₀ values of 5.3-8.5 μM as inhibitors of polymerase β in the presence of bovine serum albumin (BSA) and 2.5-4.8 μM in the absence of BSA.