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

• Published in: International journal of biological macromolecules 2022-06, Vol.211, p.653-668
• Main Authors: Hameed, Shehryar, Khan, Khalid Mohammed, Taslimi, Parham, Salar, Uzma, Taskin-Tok, Tugba, Kisa, Dursun, Saleem, Faiza, Solangi, Mehwish, Ahmed, Muhammad Hassaan Uddin, Rani, Kiran
• Format: Article
• Language: English
• Subjects: Acetylcholinesterases; Inhibition; Molecular docking; Quinoxaline; α-Amylase; α-Glucosidase
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.05.040

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. [Display omitted] •Synthetic 2-aryl quinoxaline derivatives as potential leads for anti-diabetic and anti-Alzheimer diseases.•Compounds evaluated against α-amylase, α-glucosidase, acetylcholinesterase, and butyrylcholinesterase enzymes.•Compounds exhibited potent inhibitory activities at nanomolar concentration.•Compounds with good inhibition constant, Ki value, were selected for molecular docking studies.