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 α-amylase (α-AMY), α-glucosidase (α-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 α-AMY, α-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.