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.