Evaluation of synthetic 2-aryl quinoxaline derivatives as α-amylase, α-glucosidase, acetylcholinesterase, and butyrylcholinesterase inhibitors

Abstract

Variety of 2-aryl quinoxaline derivatives 1-23 were synthesized in good yields, by reacting 1,2-phenylenediamine with varyingly substituted phenacyl bromides in the presence of pyridine catalyst. All molecules 1-23 were characterized by spectroscopic techniques and evaluated for their diverse biological potential against alpha-amylase (alpha-AMY), alpha-glucosidase (alpha-GLU), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes. Synthetic derivatives possess enhanced inhibitory potential against all enzymes at nanomolar concentrations. In particular, compound 14 was found much superior with IC50 = 294.35, 198.21, 17.04, and 21.46 nM against alpha-AMY, alpha-GLU, AChE, and BChE, respectively, as compared to standard inhibitors. Furthermore, selected potent compounds, including 3 , 4 , 8 , 14 , 15 , 17 , and 18 , were subjected to molecular docking studies to decipher the binding energies and interactions of ligands (synthetic molecules) with all four target enzymes.