Exploring new selective 3-benzylquinoxaline-based MAO-A inhibitors: design, synthesis, biological evaluation and docking studies.

Abstract In this investigation, we searched for novel MAO-A inhibitors using a 3-benzylquinoxaline scaffold based on our earlier findings. Series of N ′-(3-benzylquinoxalin-2-yl)acetohydrazide, 4a , N ′-(3-benzylquinoxalin-2-yl)benzohydrazide derivatives 4b – f , N ′-[2-(3-benzyl-2-oxoquinoxalin-1(2 H )-yl)acetyl]benzohydrazide derivatives 7a – d , (9 H -fluoren-9-yl)methyl 1-[2-(2-(3-benzyl-2-oxoquinoxalin-1(2 H )-yl)acetyl)-hydrazinyl]-2-ylcarbamate derivatives 8a – c , 2-(3-benzyl-2-oxoquinoxalin-1(2 H )-yl)- N ′-benzylidene acetohydrazide derivatives 9a – h , and ethyl 2-(3-benzyl-2-oxoquinoxalin-1(2 H )-yl)acetate derivatives 10a – e were synthesized and evaluated in vitro as inhibitors of the two monoamine oxidase isoforms, MAO-A and MAO-B. Most of the compounds showed a selective MAO-A inhibitory activity in the nanomolar or low micromolar range. Compounds 4e and 9g were the most potent derivatives with high MAO-A selectivity and their molecular docking studies were performed in order to rationalize the obtained biological result.