Mispyric acid, a new monocyclic triterpenoid with a novel skeleton from Mischocarpus pyriformis that inhibits DNA polymerase beta

Bioassay-guided fractionation using an assay to monitor DNA polymerase beta inhibition led to the isolation of-the inhibitor, mispyric acid (I), a mon ocyclic triterpenoid with a novel skeleton from Mischocarpus pyriformis Its . structure, including the relative stereochemistry, was established ori th e basis of HRMS and ID and 2D NMR. spectroscopic methods. Mispyric acid inh ibited DNA polymerase beta with an IC50 of 20 mu M in the presence of bovin e serum albumin (BSA) and 14 mu M in the absence of BSA, consistent with th e possibility that 1 may be of utility in vivo. This possibility was furthe r supported by the finding that compound 1 successfully potentiated the cyt otoxic action of bleomycin in cultured cells, reducing the number of viable cells by nearly 50% when employed at 50 mu M concentration in the presence of an otherwise nontoxic (75 nM) concentration of bleomycin. Finally, the novel structural framework of 1 suggests Mat its biosynthesis may obtain vi a a novel biogenetic pathway.