Structure-activity relationships in the induction of hepatic drug metabolism by azo compounds

Lipophilic azo compounds possessing 1-phenylazo-2-naphthol or 1-phenylazo-2-naphthylamine moieties induced cytochrome P-448 and related mono-oxygenase activities, UDP-glucuronyltransferase activity towards p-nitrophenol, glutathione-S-transferase activity towards 1-chloro-2,4-dinitrobenzene, aldehyde dehydrogenase, and menadione reductase activities. This pattern of induction by azo dyes is very similar to that by 3-methylcholanthrene. None of the hydrophilic azo compounds tested and none of the other lipophilic azo compounds tested including 4-phenylazo-1-naphthol induced these activities. It is suggested that the formation of a third six-membered ring fused to naphthalene in a phenanthrene-like arrangement by hydrogen bonding between the phenolic hydroxyl and azo nitrogen is required for induction.