DNA polymerase beta lyase inhibitors from Maytenus putterlickoides.
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.
Feng
Xizhi
X
Department of Chemistry, University of Virginia, Charlottesville 22901, USA.
Gao
Zhijie
Z
Li
Shisheng
S
Jones
Shannon H
SH
Hecht
Sidney M
SM
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002392:Catechin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019951:DNA Polymerase beta / Q000037:antagonists & inhibitors*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007630:Kenya; D008190:Lyases / Q000037:antagonists & inhibitors*; D029755:Maytenus / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C493708:30-(4'-hydroxybenzoyloxy)-11alpha-hydroxylupane-20(29)-en-3-one; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D014315:Triterpenes; D002392:Catechin; D019951:DNA Polymerase beta; D008190:Lyases