Synthesis of substituted quinazolone hydrazides: the relationship between chemical structure and monoamine oxidase inhibitory activity

Several substituted quinazolone hydrazides were synthesized to investigate their ability to inhibit rat liver mitochondrial monoamine oxidase. The monoamine oxidase activity was measured manometrically as oxygen uptake during oxidative deamination of tyramine. All quinazolone hydrazides, except 2-methyl-3-(3′-benzhydrazide)-4-quinazolone and 2-methyl-6,8-diiodo-3-(4′-phenylacetylhydrazide)-4-quinazolone, inhibited monoamine oxidase activity when used at a final concentration of 3 × 10−4 M. Substitution at position-6 or positions-6 and -8 of the quinazolone nucleus increased enzyme inhibitory power of quinazolone hydrazides. Monosubstituted quinazolone hydrazides exhibited maximum inhibitory effects while disubstitution resulted in a decrease in their ability to inhibit monoamine oxidase.