Design, synthesis, in silico docking, and DFT analysis of 1,2,3–triazoles containing quinoxaline hybrids as effective antimicrobial agents

It is crucial to create and find new, extremely powerful, broad–spectrum therapeutic medicines since the fast rise in multidrug-resistant microbial infections has become a significant worldwide concern. Because of its many biological activities, the heterocyclic framework has attracted a lot of attention. Click chemistry was used to create a novel series of quinoxaline–1,2,3–triazole derivatives using the Huisgen 1,3–dipolar cycloaddition between azide and terminal alkyne. The obtained compounds 4 ( a–k ) were isolated in moderate to good yields, and their structures were confirmed by HRMS, ¹H–NMR, ¹³C–NMR, and IR spectroscopic analyses, which clearly evidenced the formation of the acetamide–triazole ring and the expected substitution patterns. Among them, compounds 4c , 4e , 4 h , and 4j displayed the most potent inhibitory action against S. aureus , with zones of inhibition of 33 ± 1.67, 36 ± 0.93, 34 ± 1.20, and 35 ± 0.90 mm, respectively. After in vitro testing, compound 4e was identified as the most remarkable antitubercular compound, with an MIC of 2.76 ± 1.22 µ g. mL − 1 (Streptomycin had an MIC of 3.14 ± 0.55 µ g. mL − 1 ). Additionally, docking scores from molecular docking experiments demonstrate the potent compounds strong binding hydrophobic, H-bonding, and electrostatic interactions with their targets. Additionally, all of the compounds underwent ADME-Tox study to assess their pharmacokinetic characteristics, indicating that all of the compounds showed similar outcomes. The chemical nature of these compounds was revealed by performing the DFT calculations. Drug-likeness profiles showed good bioavailability, robust hydrogen bonding, and ideal logP. Favourable conformational compaction was found using docking, ADME-T, and DFT research. Therefore, 1,2,3–triazole–quinoxaline derivatives, particularly 4e , 4 h , and 4j may serve as promising candidates for the development of antimicrobial/anti-TB agents.