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

J. Z. Deng, S. R. Starck, D. A. Sun, M. Sabat, S. M. Hecht

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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 triterpenoid found to inhibit DNA polymerase β.

Original languageEnglish (US)
Pages (from-to)1356-1360
Number of pages5
JournalJournal of Natural Products
Volume63
Issue number10
DOIs
StatePublished - Nov 13 2000

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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