Triazene metabolism. II. Transportability and enzyme inhibitory characteristics of metabolites of antitumor dimethyltriazenes.
A series of dimethyltriazenes (Ar . N==N . NMe2), monomethyltriazenes (Ar . N==N . NH . Me), and triazene carbinolamines (Ar . N==N . NMe . CH2OH) have been studied for their inhibitory effects on the enzyme, hog liver esterase (EC 3.1.1.1). p-Nitrophenyl acetate was used as the model substrate and the rate of hydrolysis was followed spectrophotometrically at 400 nm, the absorption maximum of the p-nitrophenylate ion. Only triazenes with an ester group in the aryl moiety exhibited significant inhibition. Preincubation of the enzyme with the monomethyltriazene (McO2C . C6H4 . N==N . NHMe) or the methyloltriazene (MeO2C . C6H4 . N==NMe . CH2OH) gave enhanced inhibition, which was not observed when the dimethyltriazene (MeO2C . C6H4 . N==N . NMe2) was preincubated with the enzyme. Inhibition of enzyme activity by the monomethyltriazene was shown to be essentially irreversible, whereas the model substrates, methyl benzoate and methyl p-aminobenzoate, gave reversible inhibition in the same assay. The inhibition by the N-methyloltriazene was only partially reversible. . The results are discussed with relevance to the role of the monomethyltriazenes and N-methyloltriazenes as possible transportable metabolites of the antitumour dimethyltriazenes.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D004950:Esterases / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D013552:Swine; D014226:Triazenes / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D014226:Triazenes; D004950:Esterases