The relationship between the effect of biphenylcarboxylic acid analogs on glyceride synthesis and conformation

The inhibition of biphenylcarboxylic acid analogs on glyceride synthesis was studied in association with conformation of the chemicals. Chemicals used were benzoic acid substituted with phenyl, benzoyl and phenoxy groups, phenylphenyloxyacetic acid and p-phenylacetic acid. Twist angles were calculated by a molecular orbital method. Following oral administration of p-phenylbenzoic acid to the rats for 7 days, the decrease of the triglyceride synthesized from [14C]oleic acid was observed in the adipose tissue. The in vitro inhibitions on the formation of fatty acyl-CoA thioester were examined from the influence on the hippuric acid formation from [14C]benzoic acid using the rat liver slices. In the homologous series, high inhibition was observed in para and meta substituents. None, or low inhibitions of ortho-substituted chemicals were related to the steric hindrance of the phenyl ring against carboxyl groups. This hinderance was associated with conformation and with the geometrical relationship between substituted phenyl rings and carbon atoms of carboxylic acid. In the in vitro inhibition on overall formation of diglyceride and triglyceride from [14C]glycerol, o-phenylbenzoic acid showing no inhibition on hippuric acid formation did not show inhibition. However, other ortho-substituted chemicals showed higher inhibition in comparison with the inhibition on hippuric acid formation. The inhibition of para- and meta-substituted chemicals were higher than the corresponding values of ortho substituted compounds.