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

Year: 2026

Type: article

Abstract: 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.

Source: Scientific Reports

DOI: 10.1038/s41598-026-71429-x