(Hetero-)(arylidene)arylhydrazides as multitarget-directed monoamine oxidase inhibitors

Fourteen (hetero-)(arylidene)arylhydrazide derivatives (ABH1-ABH14) were synthesized, and their inhibitory activities against monoamine oxidases (MAOs) and acetylcholinesterase (AChE) were evaluated. Compound ABH5 most potently inhibited MAO-B with an IC50value of 0.025 ± 0.0019 μM; ABH2 and ABH3 exhibited high IC50values as well. Most of the compounds weakly inhibited MAO-A, except ABH5 (IC50= 3.31 ± 0.41 μM). Among the active compounds, ABH2 showed the highest selectivity index (SI) of 174 for MAO-B, followed by ABH5 (SI = 132). ABH3 and ABH5 effectively inhibited AChE with IC50values of 15.7 ± 6.52 and 16.5 ± 7.29 μM, respectively, whereas the other compounds were weak inhibitors of AChE. ABH5 was shown to be a reversible competitive inhibitor for MAO-A and MAO-B with Kivalues of 0.96 ± 0.19 and 0.024 ± 0.0077 μM, respectively, suggesting that this molecule can be considered as an interesting candidate for further development as a multitarget inhibitor relating to neurodegenerative disorders.