Synthesis of quinoxaline derivatives using different solvent systems, their potent antibacterial activities and molecular docking

In this study, a new series of quinoxaline derivatives were synthesized by the reaction of 2,3-dichloroquinoxaline with aromatic thiols, leading to the formation of 2,3-bis(arylthiol)quinoxaline, 4-chloro-12H-quinoxalino[2,3-b]1,4-benzothiazine and 5-nitro-1H-benzo[d]imidazole-2-thiol in good to excellent yields. The synthesized quinoxaline derivatives were structurally characterized using infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), elemental analysis and mass spectrometry. Their drug-like properties were evaluated using SwissADME. With the exception of compound 6, all compounds showed significant bioavailability predictions and were subsequently evaluated for their antibacterial activity. The results of the antimicrobial assays showed that the 2,3-bis(arylthiol)quinoxalines exhibited superior inhibitory activity compared to the other synthesized compounds. Further validation was provided by protein-ligand interaction studies using docking analysis. All compounds showed favourable docking values between −7.45 and −8.60 kcal/mol against DNA gyrase subunit B (DNAG) and −7.43 to −8.16 kcal/mol against penicillin-binding protein 1a (PBP1a). Compounds 5 and 6 in particular showed high docking values, confirming the antibacterial in vitro results.