Design, synthesis, in vitro, and in silico studies of 1,2,4-triazole-piperazine hybrid derivatives as potential MAO inhibitors.

[Display omitted] • 10 novel 1,2,4-Triazole-Piperazine hybrid derivatives were synthesized. • A good ADME profile were predicted for all the synthesized compounds. • The compounds 5a-c and 5e showed significant selective MAO-A inhibitory activity. • Compound 5c was determined as the most potent agent in the series. • Docking studies performed for the compound 5c. • Compound 5c properly binds to amino acids and is very close to FAD cofactor. Monoamine oxidases (MAOs) have become promising drug targets for the development of central nervous system agents. In recent research, it was shown that numerous piperazine derivatives exhibit h MAO inhibitory activity. Therefore, in this study, a novel series of 1,2,4-triazole-piperazine derivatives (5a - j) were designed, synthesized, characterized, and screened for their h MAO-A and h MAO-B inhibitory activities. When the ADME predictions were examined, it was seen that the pharmacokinetic profiles of all synthesized compounds were appropriate. Compounds 5a , 5b , 5c , and 5e , with H, F, Cl, and NO 2 groups on the 4-position of the phenyl ring, respectively, showed important MAO-A inhibitory activity. Compound 5c was found to be the most effective agent among the synthesized compounds with an IC 50 value of 0.070 ± 0.002 µM against the MAO-A enzyme. The synthesized compounds appear to support the results of other studies to design MAO inhibitors to obtain more suitable drugs, especially for neurological disorders such as depression and anxiety. [ABSTRACT FROM AUTHOR]