Thesis (M.Sc. in Pharm.)--Chulalongkorn University, 2001

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.