DNA polymerase β lyase inhibitors from Maytenus putterlickoides

During a survey of plant secondary metabolites for DNA polymerase β lyase inhibitors, we found that a crude methyl ethyl ketone extract prepared from Maytenus putterlickoides showed strong inhibition of the lyase activity of DNA polymerase β in an in vitro assay. Bioassay-guided fractionation of the extract, using an in vitro assay, resulted in the discovery of a new active principle, 30-(4‘-hydroxybenzoyloxy)-11α-hydroxylupane-20(29)-en-3-one (1), as well as a known compound, (−)-epicatechin (2). Compounds 1 and 2 exhibited DNA polymerase β lyase inhibitory activity with IC50 values of 62.8 and 18.5 μM, respectively. Compound 2 was capable of potentiating the action of the monofunctional methylating agent methyl methanesulfonate in cultured human cancer cells, consistent with the possible utility of inhibitors of this type in vivo.