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<p>The increasing prevalence of antibiotic-resistant bacterial strains necessitates the identification of new antibacterial candidates targeting essential bacterial enzymes. In this study, 60 literature-derived compounds representing triazole, hydrazone, chalcone, and furan scaffolds were evaluated using an integrated in silico workflow. The compounds were assessed for drug-likeness using SwissADME, pharmacokinetic properties using ADMETlab 3.0, toxicity profiles using ProTox-III, and binding interactions with DNA gyrase B (PDB ID: 4KFG) using AutoDock Vina. The docking protocol was validated by redocking the co-crystallized ligand into the ATP-binding pocket, and molecular dynamics simulation was performed for the top-ranked complex. Among the investigated compounds, C3 exhibited the strongest binding affinity and formed a stable interaction network involving hydrogen bonding, electrostatic interactions, and hydrophobic contacts within the DNA gyrase B binding pocket. The 50&#xa0;ns molecular dynamics simulation further supported the stability of the DNA gyrase B–C3 complex. Compounds C25, C22, and C45 were also retained as promising secondary candidates due to their favorable binding modes and interaction diversity. The results indicate that docking affinity alone is insufficient for candidate prioritization and should be interpreted together with physicochemical, pharmacokinetic, toxicity, interaction, and dynamic stability parameters. Overall, this study provides a computational prioritization of selected literature-derived compounds as potential DNA gyrase B inhibitors and supports further validation through longer molecular dynamics simulations, binding free-energy calculations, enzymatic inhibition assays, MIC determination, and experimental ADMET/toxicity evaluation.</p>

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Integrated in silico analysis of selected heterocyclic and chalcone derivatives as DNA gyrase B inhibitors: a multiparametric computational prioritization approach

  • 期刊论文

  • 发表日期：

    2026年7月23日

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  • Gulnar Atakishiyeva,
  • Shafiga Ibrahimova,
  • Sevinc Mukhtarova,
  • Shukufa Eyvazova,
  • Sima Musayeva,
  • Ilhama Hamdullayeva,
  • Naila Veysova

摘要

The increasing prevalence of antibiotic-resistant bacterial strains necessitates the identification of new antibacterial candidates targeting essential bacterial enzymes. In this study, 60 literature-derived compounds representing triazole, hydrazone, chalcone, and furan scaffolds were evaluated using an integrated in silico workflow. The compounds were assessed for drug-likeness using SwissADME, pharmacokinetic properties using ADMETlab 3.0, toxicity profiles using ProTox-III, and binding interactions with DNA gyrase B (PDB ID: 4KFG) using AutoDock Vina. The docking protocol was validated by redocking the co-crystallized ligand into the ATP-binding pocket, and molecular dynamics simulation was performed for the top-ranked complex. Among the investigated compounds, C3 exhibited the strongest binding affinity and formed a stable interaction network involving hydrogen bonding, electrostatic interactions, and hydrophobic contacts within the DNA gyrase B binding pocket. The 50 ns molecular dynamics simulation further supported the stability of the DNA gyrase B–C3 complex. Compounds C25, C22, and C45 were also retained as promising secondary candidates due to their favorable binding modes and interaction diversity. The results indicate that docking affinity alone is insufficient for candidate prioritization and should be interpreted together with physicochemical, pharmacokinetic, toxicity, interaction, and dynamic stability parameters. Overall, this study provides a computational prioritization of selected literature-derived compounds as potential DNA gyrase B inhibitors and supports further validation through longer molecular dynamics simulations, binding free-energy calculations, enzymatic inhibition assays, MIC determination, and experimental ADMET/toxicity evaluation.