Effects of acylaminopyridine derivatives and acylaniline derivatives on monoamine oxidase activity in isolated rat liver mitochondria

Abstract

The purpose of this study was to investigate the inhibitory effect and kinetics of inhibition of acylaminopyridine and acylaniline derivatives, CU-18-07, CU-18-08, CU-18-09, CU-18-10 , CU-18-11, CU-18-12 and CU-18-13, on monoamine oxidase ( MAO ) activity of rat liver mitochondria. CU-18-07, CU-18-08, CU-18-09, CU-18-10 , CU-18-11 , CU-18-12 and CU-18-13 inhibited MAO-A and MAO-B activities with low potency. In all of tested compounds, the selective inhibitory potencies of CU-18-10 for MAO-B activity, and selectivity of CU-18-12 for MAO-A activity, were higher than those of the others. CU-18-08 showed selective inhibition towards MAO-B and CU-18-10 is a non-selective MAO inhibitor but showed preferential effect on type B of MAO. On the other hand, CU-18-07, CU-18-09, CU-18-11 CU-18-12 and CU-18-13 did not showed preferential effect on specific type of MAO. Kinetics of MAO inhibition of two interesting tested compounds were also performed. Double-reciprocal plots of MAO-A and MAO-B inhibition by CU-18-08 was reversibly mixed type of competitive and non-competitive inhibition by increased Michaelis constant, Km and decreased maximum velocity of the reaction, Vmax. Kinetic analyses of MAO by CU-18-10 revealed that the interaction with MAO-B was reversibly mixed type of non-competitive and uncompetitive inhibition but interaction with MAO-A was reversibly uncompetitive, by decreased both Km and Vmax values. Overall, this finding showed structure-activity relationship that may be applied to further examination of new potential and selective inhibitors of MAO.