DNA polymerase beta lyase inhibitors from Maytenus putterlickoides.

Abstract

During a survey of plant secondary metabolites for DNA polymerase beta lyase inhibitors, we found that a crude methyl ethyl ketone extract prepared from Maytenus putterlickoides showed strong inhibition of the lyase activity of DNA polymerase beta in an in vitro assay. Bioassay-guided fractionation of the extract, using an in vitro assay, resulted in the discovery of a new active principle, 30-(4'-hydroxybenzoyloxy)-11alpha-hydroxylupane-20(29)-en-3-one (1), as well as a known compound, (-)-epicatechin (2). Compounds 1 and 2 exhibited DNA polymerase beta lyase inhibitory activity with IC50 values of 62.8 and 18.5 microM, respectively. Compound 2 was capable of potentiating the action of the monofunctional methylating agent methyl methanesulfonate in cultured human cancer cells, consistent with the possible utility of inhibitors of this type in vivo.

• Authors: Xizhi Feng, Zhijie Gao, Shisheng Li, Shannon H Jones, Sidney M Hecht
• Journal: Journal of natural products (J Nat Prod) Vol. 67 Issue 10 Pg. 1744-7 (Oct 2004) ISSN: 0163-3864 [Print] United States
• PMID: 15497954 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 30-(4'-hydroxybenzoyloxy)-11alpha-hydroxylupane-20(29)-en-3-one
• Antineoplastic Agents, Phytogenic
• Enzyme Inhibitors
• Triterpenes
• Catechin
• DNA Polymerase beta
• Lyases

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Catechin (chemistry, isolation & purification, pharmacology)
• DNA Polymerase beta (antagonists & inhibitors)
• Drug Screening Assays, Antitumor
• Enzyme Inhibitors (chemistry, isolation & purification, pharmacology)
• Humans
• Inhibitory Concentration 50
• Kenya
• Lyases (antagonists & inhibitors)
• Maytenus (chemistry)
• Molecular Structure
• Nuclear Magnetic Resonance, Biomolecular
• Plants, Medicinal (chemistry)
• Triterpenes (chemistry, isolation & purification, pharmacology)
• Tumor Cells, Cultured