Plant sterols as selective DNA polymerase β lyase inhibitors and potentiators of bleomycin cytotoxicity

Shi Sheng Li, Zhijie Gao, Xizhi Feng, Shannon H. Jones, Sidney M. Hecht

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

In a survey of crude plant extracts for DNA polymerase β lyase inhibitors, the hexanes extracts of Cladogynus orientalis, Hymenache donacifolia, and Heteropsis integerrima, and the methyl ethyl ketone extract of Acacia pilispina were found to exhibit good inhibition of the dRP lyase activity of DNA polymerase β. Bioassay-guided fractionation of these extracts led to the isolation of three DNA polymerase β lyase inhibitory phytosterols, namely stigmasterol (1) and β-sitosterol (2), isolated from the hexanes extracts, and β-sitosterol-β-D-glucoside (3), isolated from the methyl ethyl ketone extract. Compounds 1-3 inhibited the DNA polymerase β lyase activity with IC50 values of 43.6, 43.3, and 72.4μM, respectively. Compounds 1 and 2 were found capable of potentiating the action of bleomycin in cultured human tumor cells, consistent with the possibility that lyase inhibitors may find utility in vivo.

Original languageEnglish (US)
Pages (from-to)4253-4258
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume12
Issue number15
DOIs
StatePublished - Aug 1 2004
Externally publishedYes

Keywords

  • Chemotherapy
  • Enzyme inhibitors
  • Nucleic acids
  • Sterols

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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