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.
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003580:Cytochromes / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D009284:Naphthols / Q000494:pharmacology; D010105:Oxygenases / Q000096:biosynthesis; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship
D001391:Azo Compounds; D003580:Cytochromes; D009284:Naphthols; D004364:Pharmaceutical Preparations; C024336:1-phenylazo-2-naphthol; D008748:Methylcholanthrene; C043571:1-phenylazo-2-naphthylamine; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2