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.