Mispyric Acid, a New Monocyclic Triterpenoid with a Novel Skeleton from Mischocarpus pyriformis that Inhibits DNA Polymerase β

Bioassay-guided fractionation using an assay to monitor DNA polymerase β inhibition led to the isolation of the inhibitor, mispyric acid ( 1 ), a monocyclic triterpenoid with a novel skeleton from Mischocarpus pyriformis . Its structure, including the relative stereochemistry, was established on the basis of HRMS and 1D and 2D NMR spectroscopic methods. Mispyric acid inhibited DNA polymerase β with an IC 50 of 20 μ M in the presence of bovine serum albumin (BSA) and 14 μ M in the absence of BSA, consistent with the possibility that 1 may be of utility in vivo. This possibility was further supported by the finding that compound 1 successfully potentiated the cytotoxic action of bleomycin in cultured cells, reducing the number of viable cells by nearly 50% when employed at 50 μM concentration in the presence of an otherwise nontoxic (75 nM) concentration of bleomycin. Finally, the novel structural framework of 1 suggests that its biosynthesis may obtain via a novel biogenetic pathway.