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

Missioui M., Mortada S., Guerrab W., Demirtas G., Mague J. T., Ansar M., ...More

ARABIAN JOURNAL OF CHEMISTRY, vol.15, no.6, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 15 Issue: 6
  • Publication Date: 2022
  • Doi Number: 10.1016/j.arabjc.2022.103851
  • Journal Name: ARABIAN JOURNAL OF CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Compendex, INSPEC, Directory of Open Access Journals
  • Keywords: Quinoxaline, 1,2,3-triazole, XRD, Hirshfeld Surface Analysis, (HSA), DFT, Anti-diabetic activity, Molecular docking, ALPHA-GLUCOSIDASE INHIBITORS, BIOLOGICAL-ACTIVITY, INTERMOLECULAR INTERACTIONS, TRIAZOLE DERIVATIVES, CRYSTAL-STRUCTURE, CLICK CHEMISTRY, STEEL CORROSION, MILD-STEEL, ANTICANCER, ANTIOXIDANT
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

In an effort to develop a potent antidiabetic drug, new quinoxaline derivative, 2-(4-((3methyl-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, 1 H &13 C 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 p-p 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 a-glucosidase and a-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. similar to 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).