A new 7,8-euphadien-type triterpenoid from Brackenridgea nitida and Bleasdalea bleasdalei that inhibits DNA polymerase β.

Bioassay-guided fractionation of extracts prepared from Brackenridgea nitida and Bleasdalea bleasdalei, using an assay to detect DNA polymerase β inhibition, resulted in the isolation of the inhibitory principle, (24E)-3β-hydroxy-7,24-euphadien-26-oic acid (1), a new euphane triterpenoid. The structure of 1 was established on the basis of HRMS and 1D and 2D NMR spectroscopic methods and was confirmed further by X-ray crystallographic analysis. Compound 1 inhibited rat DNA polymerase β with an IC50 value of 23 μM in the presence of bovine serum albumin (BSA) and 9.7 μM 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 1 potentiated the inhibitory action of the anticancer drug bleomycin in cultured P-388D1 cells, reducing the number of viable cells by 48% when employed at a concentration of 25 μM in the presence of an otherwise nontoxic (75 nM) concentration of bleomycin. Compound 1 is the first euphane-type tr...