<i>In silico</i> screening of dicoumarols as potential <i>Mur B</i> enzyme inhibitors in <i>Mycobacterium tuberculosis</i> : molecular docking, ADME, QSAR and MD simulations

UDP-N-acetylenolpyruvoylglucosamine reductase (<i>Mur B)</i> from <i>Mycobacterium tuberculosis</i> has gathered significant pharmaceutical interest as a pivotal target because of its essential role in bacterial viability. This study employed computational methods to screen and assess the inhibitory potential of dicoumarol derivatives against the <i>Mur B</i> protein. A diverse set of dicoumarols, sourced from PubChem and Zinc database, is subjected to molecular docking, ADME studies, and MD simulations to elucidate interacting modes and stability. A QSAR model was constructed for dicoumarol derivatives based on known inhibitor MIC values against <i>Staphylococcus aureus</i> and <i>Mur B</i>. The four best dicoumarols (<b>CID142097979, CID54716867, CID91962283, CID54705236</b>) aligned well with the model. Subsequently, these dicoumarols were scrutinized <i>via</i> 200 ns MD simulations and MM-PBSA analysis to assess their complex stability with <i>Mur B</i> protein. Various MD simulation parameters such as RMSD, RMSF, Rg, H-bonds, PCA, and FEL were employed. The 200 ns MD simulation analysis outcomes indicated that the <b><i>Mur B-</i>CID54705236</b> complex exhibited the highest stability and possessed the binding energy of -59.96 kcal/mol further verifying its stability. The post-dynamic simulation analysis showed four hydrogen bond formations with Ser70, Asn71, Leu72 and Gln137 residues at the active site of <i>Mur B</i>. Overall, these results underscored dicoumarol derivatives as potential <i>Mur B</i> inhibitors and these findings can serve as a basis for further <i>in vitro</i> studies against <i>Mur B</i> protein.