Khan_2023_J.Mol.Struct_1284_135351

Analogues of isatin/bis-Schiff bases based on thiocarbohydrazone (1-16) were synthesized, characterised using various methods like NMR and HR-ESI-MS, and then tested against the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All analogues showed good inhibitory potentials ranging from 0.20 +/- 0.05 to 7.40 +/- 0.20 M (for AChE) and 0.50 +/- 0.05 to 9.40 +/- 0.10 M (for BuChE) as compared to the reference drug Donepezil (IC50 = 2.16 +/- 0.12 & 4.5 +/- 0.11 M respectively). Analogue 1 was shown to be the most effective inhibitor of the AChE and BuChE enzymes among the synthesised analogues. The reason for Analogue 1 may be due to the role played by oxygen and the nitro motif in H-bonding with the active sites of AChE and BuChE enzymes. A structure-activity relationship (SAR) was developed based on nature, position, number, and the electron-donating and -withdrawing effects of substitution(s) on phenyl rings. Molecular docking studies were used to describe the binding interactions of the most active inhibitors with the active sites of AChE and BuChE.