Novel quinoxaline derivatives of 2, 3-diphenylquinoxaline-6-carbaldehyde and 4, 4′-(6-methylquinoxaline-2,3-diyl)bis(N,N-diphenylaniline): Synthesis, structural, DFT-computational, molecular docking, antibacterial, antioxidant, and anticancer studies

Abstract

The quinoxaline derivatives of 2, 3-diphenylquinoxaline-6-carbaldehyde (DPQC) and 4, 4′-(6-methylquinoxaline-2,3-diyl)bis(N,N-diphenylaniline) (MDBD) were synthesized using direct condensation methods, and various spectral analysis were characterized by experimental and ab initio Density functional theory (DFT) theoretical methods at the B3LYP level with 6–311++G(d,p) basis sets were used for the different spectrum analysis, which included UV-Visible, Fourier-transform infrared spectroscopy (FTIR), and 1H and 13C nuclear magnetic resonance (NMR) chemical shifts. Furthermore, for these title molecules, Nonlinear Optical (NLO) was utilized to compute first-order hyperpolarizability (β) and Mulligan population analysis was performed. The ESI-Mass spectrum analysis was performed for these quinoxaline derivatives. In this study, title molecules of DPQC and MDBD were tested for in vitro antibacterial, antioxidant, and anticancer properties which exhibited enhanced biological activities. In particular, the title molecule MDBD gave enhanced anticancer activity at the lowest concentration of 125 µg/mL against human liver cancer (HepG2) cell lines, as well as potent bactericidal activity with a maximum of (19.5 ± 1.0 mm) at 2.5 µg/mL against Yersinia enterocolitica (MTCC 840). In an (H2O2) scavenging study, MDBD revealed potent antioxidant activity (64.21%). The DPPH radical scavenging antioxidant activity of MDBD was discovered at (67.48 %) concentration at 500 µg/mL. The best binding energy between anticancer target protein, specifically c-Met-kinase (hepatocyte growth factor; PDB ID: 3F66) and DPQC and MDBD compounds, were determined using in silico molecular docking. The auto dock software provided superior results for the title compound MDBD, which exhibited a higher ligand-receptor interaction energy value of -10.8 (kcal/mol) against 3F66 protein and a 0.01187 µM inhibition constant (ki) with (active site A) presented amino acids such as A: ARG1086, A: MET1211, A: VAL1092, A: ALA1226, A: ALA1108, A: MET1211. Further, studies are warranted to explore their promising anticancer and other pharmacological and biochemical properties.