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 Hecht

Research output: Contribution to journalArticle

31 Citations (Scopus)

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

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DNA-Directed DNA Polymerase
Bovine Serum Albumin
Skeleton
DNA
Stereochemistry
Acids
Bioassay
Biosynthesis
Bleomycin
Fractionation
Biological Assay
Inhibitory Concentration 50
Cultured Cells
Assays
Cell Count
Cells
Nuclear magnetic resonance
mispyric acid
indium-bleomycin

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Mispyric acid, a new monocyclic triterpenoid with a novel skeleton from Mischocarpus pyriformis that inhibits DNA polymerase β. / Sun, Di An; Deng, Jing Zhen; Starck, Shelley R.; Hecht, Sidney.

In: Journal of the American Chemical Society, Vol. 121, No. 26, 07.07.1999, p. 6120-6124.

Research output: Contribution to journalArticle

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