Harbinatic acid, a novel and potent DNA polymerase beta inhibitor from Hardwickia binata.
Bioassay-guided fractionation of an active methyl ethyl ketone extract of Hardwickia binata, using an assay sensitive to DNA polymerase beta inhibition, resulted in the isolation of a potent inhibitor. This proved to be a novel diterpenoid, which has been named harbinatic acid (1). The structure of 1 was established as 3alpha-O-trans-p-coumaroyl-7-labden-15-oic acid from spectroscopic analysis and by comparison with the published data for a structurally related compound. Compound 1 strongly inhibited calf thymus DNA polymerase beta, with an IC(50) value of 2.9 microM.
Deng
J Z
JZ
Departments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901, USA.
Starck
S R
SR
Hecht
S M
SM
Ijames
C F
CF
Hemling
M E
ME
D019951:DNA Polymerase beta / Q000037:antagonists & inhibitors*; D004224:Diterpenes / Q000302:isolation & purification* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D007887:Fabaceae / Q000737:chemistry*; D007194:India; D009682:Magnetic Resonance Spectroscopy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010946:Plants, Medicinal
D004224:Diterpenes; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C121575:harbinatic acid; D019951:DNA Polymerase beta