Greener pastures in evaluating antidiabetic drug for a quinoxaline Derivative: Synthesis, Characterization, Molecular Docking, in vitro and HSA/DFT/XRD studies

• Published in: Arabian journal of chemistry Vol. 15; no. 6; p. 103851
• Main Authors: Missioui, Mohcine, Mortada, Salma, Guerrab, Walid, Demirtaş, Güneş, Mague, Joel T., Ansar, M'hammed, El Abbes Faouzi, My, Essassi, E.M., Mehdar, Yassin T.H., Aljohani, Faizah S., Said, Musa A., Ramli, Youssef
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.06.2022; Elsevier
• Subjects: 1,2,3-triazole; Anti-diabetic activity; Hirshfeld Surface Analysis (HSA), DFT; Molecular docking; Quinoxaline; XRD; Quinoxaline; XRD; Anti-diabetic activity; Hirshfeld Surface Analysis (HSA), DFT; 1,2,3-triazole; Molecular docking
• ISSN: 1878-5352; 1878-5379
• DOI: 10.1016/j.arabjc.2022.103851

The physicochemical, pharmacokinetic and toxicological properties of MOQTA have been evaluated. [Display omitted] •A new quinoxaline containing triazole MOQTA is prepared via azide − alkynecycloaddition“click” procedure.•TheMOQTA is characterized by XRD andDFT.•Frontier Molecular Orbitals (FMOs) and Molecular Electrostatic Potential (MEP) surfaces of MOQTA were generated.•Hirshfeld surface analysis (HSA) and 2D fingerprint plots were presented.•Compound MOQTA has moderate anti-diabetic activity and excellent anti-oxidant activity.•Molecular docking were carried to examine the binding mode between MOQTA and α-glucosidase / α-amylase. In an effort to develop a potent antidiabetic drug, new quinoxaline derivative, 2-(4-((3-methyl-2-oxoquinoxalin-1(2H)-yl)methyl)-4,5-dihydro-1H-1,2,3-triazol-1-yl)-N-(p-tolyl)acetamide (MOQTA) was synthesized and characterized by XRD and various spectroscopic tools (IR, 1H &13C NMR, ESI-MS). The geometric optimization of the molecule was calculated with Density Functional Theory (DFT) method by B3LYP with a 6–311++G(d,p) basis set. Frontier Molecular Orbitals (FMOs) and Molecular Electrostatic Potential (MEP) surfaces of the title compound were generated. Furthermore, Hirshfeld surface analysis (HSA) and 2D fingerprint plots were presented. The calculated MEP and HSA surface interactions were compared in terms of hydrogen bonds and π-π stacking interactions obtained by X-ray packing analyses. X-ray crystallographic structure analysis revealed that the N—HN, C—HO and C—HN intermolecular hydrogen bonds were in agreement with those obtained by HSA. Moreover, MOQTA was assessed for its in vitro anti-diabetic activity. Likewise, molecular docking analyses were conducted to examine the binding mode between MOQTA and the enzymes α-glucosidase and α-amylase. Finally, the physicochemical, pharmacokinetic and toxicological properties of MOQTA have been evaluated by using in silico absorption, distribution, metabolism, excretion and toxicity analysis prediction.