Microbial-based natural products as potential inhibitors targeting DNA gyrase B of

Introduction: Since the emergence of Methods: In the present study, multiple computational tools were adopted to screen a microbial-based natural products database (NPAtlas) for potential inhibitors of the ATPase activity of MBT DNA gyrase. Results and discussion: Twelve hits were initially identified as the top candidates based on their docking scores (ranging from -9.491 to -10.77 kcal/mol) and binding free energies (-60.37 to -73.21 kcal/mol). Following this, computational filters, including ADME-T profiling and pharmacophore modeling, were applied to further refine the selection. As a result, three compounds 1-Hydroxy-D-788-7, Erythrin, and Pyrindolol K2 emerged as the most promising, exhibiting favorable drug-like properties. Notably, 1-Hydroxy-D-788-7, an anthracycline derivative, demonstrated superior binding affinity in molecular dynamics simulations. The RMSD values, ranging from 1.7 to 2.5 Å, alongside RMSF analysis and a detailed evaluation of the established interaction forces, revealed that 1-Hydroxy-D-788-7 was the strongest binder to Mycobacterial DNA Gyrase B. The stable binding and favorable interaction profile highlighted 1-Hydroxy-D-788-7 as a top hit. These comprehensive computational findings strongly support the potential of 1-Hydroxy-D-788-7 as an effective anti-TB lead compound, warranting further experimental validation to confirm its therapeutic efficacy.