Induction of hepatic microsomal drug metabolism by azo compounds: a structure-activity relationship.
The structure-activity relationship of 40 azo compounds in their ability to induce cytochrome P-448 and associated monooxygenase activities, as well as UDP-glucuronyltransferase (UDPGT) activity, was investigated. Regardless of their structure, hydrophilic azo dyes and lipophilic azobenzene derivatives were not able to induce these enzyme activities. Only those lipophilic azo dyes with 1-azo-2-naphthol or 1-azo-2-naphthylamine moieties were able to induce cytochrome P-448 and related monooxygenase activities, as well as UDPGT activity. The extent of induction is comparable to or greater than that caused by 3-methylcholanthrene (3-MC). It is suggested that those azo dyes capable of inducing P-450 type cytochromes can form coplanar structures with three fused, 6-membered rings through intramolecular hydrogen bonding. These structures are analogous to polycyclic aromatic hydrocarbons that can also induce.
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D004396:Coloring Agents; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003580:Cytochromes / Q000096:biosynthesis*; D004790:Enzyme Induction; D014453:Glucuronosyltransferase / Q000096:biosynthesis*; D007700:Kinetics; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D001391:Azo Compounds; D004396:Coloring Agents; D003580:Cytochromes; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D014453:Glucuronosyltransferase; D010634:Phenobarbital