The interaction of arylalkybenzimidazoles and related compounds with microsomal oxidation.
A series of 2-arylalkyl- and 2-(4'-alkyl)phenoxymethylbenzimidazoles was synthesized and evaluated as inhibitors of mixed-function oxidase activity in phenobarbitone- and beta-naphthoflavone-induced rat liver microsomes. Higher homologues of the 2-arylalkyl series were more potent inhibitors than lower homologues against all mono-oxygenase activities except aniline p-hydroxylation. Smaller 2-substituents were associated with relatively low-affinity reverse type I spectral binding behaviour, whereas larger substituents were associated with type I binding of high affinity.
D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors; D000815:Aniline Hydroxylase / Q000037:antagonists & inhibitors; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D001562:Benzimidazoles / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D019324:beta-Naphthoflavone
D001562:Benzimidazoles; D001571:Benzoflavones; D065607:Cytochrome P-450 Enzyme Inhibitors; D019324:beta-Naphthoflavone; D006899:Mixed Function Oxygenases; D000815:Aniline Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D000633:Aminopyrine N-Demethylase; D010634:Phenobarbital