Synthesis of N′-(4-/3-/2-/Non-substituted benzylidene)-4-[(4-methylphenyl)sulfonyloxy] Benzohydrazides and Evaluation of Their Inhibitory Activities against Monoamine Oxidases and β-Secretase

Nineteen tosylated acyl hydrazone derivatives were synthesized, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-secretase (BACE-1) evaluated. Compound 3o was the most potent inhibitor of MAO-A, with an IC50 value 1.54 µM, followed by 3a (IC50 = 3.35 µM). A structural comparison indicated that 3-F group in increased its activity MAO-A. 3s MAO-B, 3.64 3t 5.69 The MAO-B order 3- > 4- 2-NO2 groups 3s, 3t, 3r, respectively. All compounds weakly inhibited AChE BChE, which retained >50% residual at 10 except for 3a, BChE 16.1 µM. Interestingly, 3e, 3f, 3n BACE-1 values 8.63, 9.92, 8.47 respectively, lower than quercetin reference. Compounds found to be reversible competitive inhibitors MAO-A Ki 0.35 ± 0.074 1.97 0.65 Moreover, effective inhibitors. lead molecules further investigated molecular docking studies elucidate binding interactions target enzymes.