Effects of 2-arylbenzimidazoles on rat hepatic microsomal monooxygenase system

Abstract

1. The effects of eight newly synthesized 2-aryl substituted benzimidazole derivatives on control and phenobarbital (PB) treated rat liver microsomal aniline 4-hydroxylase and ethylmorphine N-demethylase activities, and their binding to control and PB-treated rat liver microsomal oxidized cytochrome P-450 are presented. 2. All compounds inhibited ethylmorphine N-demethylase activity with I 50 values ranging from 8.50 × 10 −4 M to 27.83 × 10 −4 M in control and ranging from 2.80 × 10 −4 M to 15.79 × 10 −4 M in PB-treated rats. 3. Aniline 4-hydroxylase activity was inhibited by all of the compounds tested having I 50 values in the range of 7.04 × 10 −4 M-31.37 × 10 −4 M in PB-treated rats, but only five of the compounds showed inhibitory activity in control rats. 4. Only a few significant regression coefficients could be found between the parameters of the chemicals studied and their inhibitory patterns. 5. No correlation has been observed between the binding of the derivatives and their inhibitory pattern.