INTERACTION OF INDOLE-DERIVATIVES WITH MONOAMINE-OXIDASE-A AND MONOAMINE-OXIDASE-B - STUDIES ON THE STRUCTURE-INHIBITORY ACTIVITY RELATIONSHIP

Indole and isatin (2,3-dioxindole) analogues were studied as inhibitor s of MAO-A and B. They exhibited reversible and competitive MAO inhibi tion. Three dimensional structures of the compounds tested were constr ucted and minimized using PC-based molecular graphic software. The QSA R analysis revealed the requirement of co-planar structure of substitu ents at C2 and C3 of indole ring for selective MAO-A inhibition, whils t type of bond was less essential. The presence of hydroxy group at C5 of isatin increased selectivity of MAO-A inhibition, however simultan eous insertion of substituents into both positions of indole ring (5-h ydroxy-2-phenylindole) led to a decrease of MAO-A inhibition. The plan ar molecules demonstrating potent MAO-A inhibition have the average si zes 7 Angstrom in length and 6 Angstrom in width. The MAO B inhibition also depended on the sizes of planar molecules however distribution o f electron density in the molecules was another precondition for the s elective inhibition of the enzyme.