Novel anti-inflammatory compounds from Myrsine seguinii, terpeno-benzoic acids, are inhibitors of mammalian DNA polymerases

Abstract

Novel anti-inflammatory compounds, terpeno-benzoic acids, were found from the plant, Myrsine seguinii. The strongest of these anti-inflammatory agents, 3-geranyl-4-hydroxy-5-(3′-methyl-2′-butenyl) benzoic acid (compound 1), showed an inhibitory effect against enzymes involved in replication, such as calf DNA polymerase α (pol. α), rat DNA polymerase β (pol. β) and one of the β family polymerases, calf thymus terminal deoxynucleotidyl transferase (TdT). The minimum inhibitory concentration (MIC) and IC 50 values were 82 and 22 μM for pol. α, 86 and 11 μM for pol. β, 140 and 46 μM for TdT, respectively. However, compound 1 did not influence the activities of plant DNA polymerases, human immunodeficiency virus type-1 reverse transcriptase, any of the prokaryotic DNA polymerases or DNA and RNA metabolic enzymes tested. Dose-dependent relationships were observed between the anti-inflammatory activities and the DNA polymerase-inhibitory activities of the four derivatives. The carboxylic acid moiety in the benzoic acid of the compounds appeared to be related to the inhibitory effects. The mode of action of the terpeno-benzoic acids against the polymerases and their relationships to the anti-inflammatory activity are discussed.