In vitro interaction of 6-iodo-4-oxo-quinazoline derivatives with cytosolic molybdenum hydroxylases

Abstract

In the present study 27 different quinazoline derivatives have been synthesized and investigated as substrate or inhibitor for molybdenum hydroxylases. These compounds have been identified using NMR, mass spectrum, infrared and elementary analysis. In vitro^ the oxidation of xanthine and phthalazine by xanthine oxidase and aldehyde oxidase from guinea pig liver, respectively, had been inhibited notably by 6-iodo-quinazolines. Although xanthine and phthalazine are excellent and specific substrates, allopurinol (100 uM) and menadione (100 uM) as specific inhibitors of xanthine oxidase and aldehyde oxidase, respectively, have been used to characterize the specificity of reaction. The inhibitory specificity as well as the active site requirements have been discussed and compared with their relative lipophilicities. 6-Iodo-substituted quinazolines inhibit both aldehyde oxidase and xanthine oxidase in a competitive pattern with Kj or ICS0 ranging from 48 to 700 uM. This study indicates strongly that un-fused pyrimidine ring is required for inhibitory activity of quinazoline derivatives.