New styrylquinoxaline: synthesis, structural, biological evaluation, ADMET prediction and molecular docking investigations

Abstract

The organic compound (E)-3-(4-methylstyryl)quinoxalin-2(1H)-one (SQO) with molecular formula C₁₇H₁₄N₂O was synthesized and analyzed using single crystal X-ray diffraction, ¹H, ¹³C NMR and FTIR spectroscopic techniques. The geometric parameters of the molecule was optimized by density-functional theory (DFT) choosing B3LYP with 6-31++G(d,p) basis set. For compatibility, the theoretical structure and experimental structure were overlapped with each other. Frontier molecular orbitals of the title compound were made, and energy gap between HOMO and LUMO was calculated. Molecular electrostatic potential map was generated finding electrophilic and nucleophilic attack centers using DFT method. Hirshfeld surface analysis (HSA) confirms active regions at the circumference of N1 atoms and O1 atoms that form intermolecular N1—H1···O1 hydrogen bond. The acute oral toxicity study was carried out according to OECD guideline, which approve that the compound SQO was non-toxic. In addition, this quinoxaline derivative was evaluated for its in vitro antidiabetic activity against α-glucosidase and α-amylase enzymes and for antioxidant activity by utilizing several tests as 1,1-diphenyl-2-picryl hydrazyl, (2,2′-azino-bis(3-ethyl benzthiazoline-6-sulfonicacid), reducing power test (FRAP) and hydrogen peroxide activity H₂O₂. The molecular docking studies were performed to investigate the antidiabetic activity of SQO and compared with the experimental results. SQO is a potent antidiabetic from both the experimental and molecular docking results. Finally, the physicochemical, pharmacokinetic and toxicological properties of SQO have been evaluated by using in silico absorption, distribution, metabolism, excretion and toxicity analysis prediction.

Keywords:

• Quinoxaline
• energy gap
• DFT calculations
• Hirshfeld surface analysis
• antidiabetic activity
• molecular docking

Acknowledgment

Authors thank Tulane University for support of the Tulane Crystallography Laboratory.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Authors thank Mohammed V University and the Ondokuz Mayıs University Research Fund for financial support for this study. The support of NSF-MRI Grant no. 1228232 for the purchase of the diffractometer is greatly acknowledged.