DNA polymerase beta inhibitors from Baeckea gunniana.

J Nat Prod (1999), Volume 62, Page 1624

Abstract:

Crude plant extracts were surveyed for their ability to inhibit DNA polymerase beta. 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 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 established as 3 beta-hydroxyrus-12,19(29)-dien-28-oic acid (1) and 3 beta-hydroxyrus-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 beta inhibitor was oleanolic acid (3). Compounds 1-4 had IC50 values of 5.3-8.5 microM as inhibitors of polymerase beta in the presence of bovine serum albumin (BSA) and 2.5-4.8 microM in the absence of BSA.

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