Synthesis, molecular docking, binding free energy calculation and molecular dynamics simulation studies of benzothiazol-2-ylcarbamodithioates as <i>Staphylococcus aureus</i> MurD inhibitors JupudiSrikanth AzamMohammed Afzal WadhwaniAshish 2019 <p>A new series of benzothiazol-2-ylcarbamodithioate functional compounds <b>5a-f</b> has been designed, synthesized and characterized by spectral data. These compounds were screened for their <i>in vitro</i> antibacterial activity against strains of <i>Staphylococcus aureus</i> (NCIM 5021, NCIM 5022 and methicillin-resistant isolate 43300), <i>Bacillus subtilis</i> (NCIM 2545), <i>Escherichia coli</i> (NCIM 2567), <i>Klebsiella pneumoniae</i> (NCIM 2706) and <i>Psudomonas aeruginosa</i> (NCIM 2036). Compounds <b>5a</b> and <b>5d</b> exhibited significant activity against all the tested bacterial strains. Specifically, compounds <b>5a</b> and <b>5d</b> showed potent activity against <i>K. pneumoniae</i> (NCIM 2706), while compound <b>5a</b> also displayed potent activity against <i>S. aureus</i> (NCIM 5021). Compound <b>5d</b> showed minimum IC<sub>50</sub> value of 13.37 μM against <i>S. aureus</i> MurD enzyme. Further, the binding interactions of compounds <b>5a-f</b> in the catalytic pocket have been investigated using the extra-precision molecular docking and binding free energy calculation by MM-GBSA approach. A 30 ns molecular dynamics simulation of <b>5d</b>/modeled <i>S. aureus</i> MurD enzyme was performed to determine the stability of the predicted binding conformation.</p>