Novel antioxidant quinoxaline derivative: Synthesis, crystal structure, theoretical studies, antidiabetic activity and molecular docking study

Abstract

New quinoxaline derivative, N-(4-methyl-2-nitrophenyl)-2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamide (NPOQA) has been synthesized and characterized by IR, 1H &13C NMR, ESI-MS and single crystal X-ray diffraction analysis using experimental and theoretical methods. The thermodynamic quantities and quantum chemical parameters were predicted by using B3LYP/6–311G** level to investigate the physical and electronic properties of the compound. Frontier Molecular Orbital “FMO” and Natural Bond Orbital “NBO” analyses of the compound were performed to enligten the possible rectivity trend and intramolecular interactions contibuted to the decreasing of the stabilization. In addition, the newly synthesized compound was evaluated for its in vitro antidiabetic activity against α-glucosidase and α-amylase enzymes and for antioxidant activity by utilizing several tests as DPPH (1, 1-diphenyl-2-picryl hydrazyl), ABTS (2, 2′-azino-bis(3-ethyl benzthiazoline-6-sulfonicacid), reducing power test (FRAP) and Hydrogen Peroxide Activity H2O2. Finally, Molecular docking studies were performed to investigate the binding mode between the quinoxaline derivative NPOQA and α-glucosidase and α-amylase. Docking calculations showed an important binding affinity as compared to standard drug acarbose, -6.5 and -6.9 kcal/mol successively for α-glucosidase and α-amylase, which are in agreement with the results of in vitro studies.