EXPERIMENTAL AND THEORETICAL-STUDY OF REVERSIBLE MONOAMINE-OXIDASE INHIBITORS - STRUCTURAL APPROACH OF THE ACTIVE-SITE OF THE ENZYME

Experimental and theoretical physico-chemical methods were used to inv estigate the interaction between aryl-oxazolidinones and monoamine oxi dase (MAO). Several arguments suggest that these compounds interact wi th the flavin adenine dinucleotide (FAD) cofactor of MAO. The calculat ion using ab initio molecular orbital methods of the electronic proper ties of flavin and befloxatone, a reversible inhibitor of MAO A, led t o a description of the interaction between aryl-oxazolidinones and the cofactor of the enzyme. Structure activity relationship results revea led additional sites of interaction with the protein core of MAO A. As a result of this work, a model is proposed for the reversible inhibit ion of MAO by oxazolidinones via long distance, reversible interaction s with the FAD cofactor of the enzyme.