(Hetero-)(arylidene)arylhydrazides as Multitarget-Directed Monoamine Oxidase Inhibitors

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2020-10-13 DOI:10.1021/acscombsci.0c00136

Ashique Palakkathondi, Jong Min Oh, Sanal Dev, T. M. Rangarajan, Swafvan Kaipakasseri, Fathima Sahla Kavully, Nicola Gambacorta, Orazio Nicolotti, Hoon Kim*, Bijo Mathew*

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引用次数: 5

Abstract

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 IC₅₀ value of 0.025 ± 0.0019 μM; ABH2 and ABH3 exhibited high IC₅₀ values 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 IC₅₀ values 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 K_i values 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.