Biological evaluation and molecular docking studies of 4-aminobenzohydrazide derivatives as cholinesterase inhibitors

Abstract

• Synthesis of mono and disubstituted 4-amino benzohydrazides. • Evaluating the 4-amino benzohydrazide derivative compounds as a potential acetylcholinesterase and butyrylcholinesterase inhibitors. • Molecular docking analyze of 4-amino benzohydrazide derivative compounds in active site of acetylcholinesterase and butyrylcholinesterase. Nowadays, inhibition of the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes have emerged as an encouraging approach in the treatment of dementia and remission of symptoms of Alzheimer's disease. Therefore, inhibition of cholinesterases is one of the main targets by researchers. Benzohydrazides are biologically active compounds and have various pharmacological effects, bearing these in mind, we investigated the inhibitory effects of some mono or di-substituted 4-aminobenzohydrazide derivatives (1a-11a) against AChE and BChE. For this purpose, we studied the inhibition effects (IC 50 , K i values, and inhibition types) of these molecules on AChE and BChE enzymes. Based on the results, compound 3a showed potent AChE and BChE inhibition (IC 50 = 0.59 and 0.15 μM). The K i values of the compounds ( 3a, 4a, and 8a ) showing the best inhibition effect against AChE and BChE were calculated and these values ranged from 0.10 ± 0.04 to 5.10 ± 2.14 μM. To determine the possible binding mechanisms with the active sites of both enzymes of compounds 3a, 4a , and 8a having strong inhibitory effects, docking analyses were performed. According to the docking results, compound 3a showed the best binding affinity (-7.3 kcal/mol for AChE and -6.8 kcal/mol for BChE) against both enzymes.