The role of aldehyde oxidase in the in vivo metabolism of benzothiazole.

Thiazoles and benzothiazoles form part of the molecular structure of many drugs, biocides and industrial chemicals. Examples include 2-mercaptobenzothiazole which is widely used as a rubber accelerator in the manufacture of tyres and which as a consequence occurs in street runoff and esturine sediments [ l ] and which may have ecotoxicological importance. In spite of this widespread occurrence of the thiazole ring in biological systems little is known of its susceptibility to metabolism. We have previously reported [2] that in the guinea pig, benzothiazole is metabolised to three major metabolites: 2-methylmercaptoaniline [I], 2-methylsulphinylaniline [11] and 2-methylsulphonylaniline [III]. The formation of these metabolites implied preliminary cleavage of the thiazole ring probably involving initial nucleophilic attack at the C-2 position. Possible enzymes responsible for this cleavage are the molybdenum oxidases aldehyde oxidase and xanthine oxidase which are known to promote nucleophilic attack at an electron-deficient carbon atom adjacent to a ring nitrogen atom [3,4]. We have therefore investigated the possible role of aldehyde oxidase and of 2-hydroxybenzothiazole in the metabolic ring cleavage of benzothiazole in the guinea pig.