In silico molecular modeling and invitro biological screening of novel benzimidazole-based piperazine derivatives as potential acetylcholinesterase and butyrylcholinesterase inhibitors.

Abstract

New series of benzimidazole incorporating piperazine moieties in single molecular framework has been reported. The structures of the synthesized derivatives were assigned by 1H-NMR, 13C-NMR, and HR-MS techniques. The hybrid derivatives were evaluated for their acetylcholinesterase and butyrylcholinesterase inhibition effect. All the synthesized analogs showed good to moderate inhibitory effect ranging from IC50 value 0.20±0.01 µM to 0.50±0.10 µM for acetylcholinesterase and from IC50 value 0.25±0.01 µM to0.70±0.10 µM for butyrylcholinesterase except one thatshowed least potency with IC50 value 1.05±0.1 µM and 1.20±0.1 µM. The differences in inhibitory potential of synthesized compounds were due to the nature and position of substitution attached to the main ring. Additionally, molecular docking study was carried out for most active inorder to explore the binding interactions established byligand (active compounds) with the active residues of targeted AChE & BuChE enzyme.