Abstract
Alzheimer’s is a type of dementia that affects the affected person’s thinking, memory, and behavior. It is a multifactorial disease, developed by the breakdown of the neurotransmitter acetylcholine via acetylcholinesterase (AChE). The present study was designed to evaluate potential inhibitors of acetylcholinesterase that could be used as a therapeutic agent against Alzheimer’s disease (AD). For this course, synthetic compounds of the Schiff bases class of 2-mercaptobenzimidazole hydrazone derivatives (
9–14
) were determined to be potent acetylcholinesterase inhibitors with IC
50
values varying between 37.64 ± 0.2 and 74.76 ± 0.3 μM. The kinetic studies showed that these are non-competitive inhibitors of AChE. Molecular docking studies revealed that all compounds accommodate well in the active site and are stabilized by hydrophobic interactions and hydrogen bonding. Molecular dynamics (MD) simulations of selected potent inhibitors confirm their stability in the active site of the enzyme. Moreover, all compounds showed antispasmodic and Ca
2+
antagonistic activities. Among the selected compounds of 2-mercaptobenzimidazole hydrazone derivatives, compound
11
exhibited the highest activity on spontaneous and K
+
-induced contractions, followed by compound
13
. Therefore, the Ca
2+
antagonistic, AChE inhibition potential, and safety profile of these compounds in the human neutrophil viability assay make them potential drug candidates against AD in the future.