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

Di An Sun, Jing Zhen Deng, Shelley R. Starck, Sidney M. Hecht

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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 IC50 of 20 μM in the presence of bovine serum albumin (BSA) and 14 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 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.

Original languageEnglish (US)
Pages (from-to)6120-6124
Number of pages5
JournalJournal of the American Chemical Society
Volume121
Issue number26
DOIs
StatePublished - Jul 7 1999
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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