Some substituted thioureas 6a-i containing 1,3,4-thiadiazole ring were synthesized by reaction of corresponding different substituted 2-amino-1,3,4-thiadiazoles 3a-i with p-toluenesulfonyl isocyanate in one-pot procedure. The antibacterial as well as antifungal activities of these sulfonyl thioureas were estimated using minimum inhibitory concentration protocol. Almost all of thioureas exhibited remarkable antimicrobial activity. Amongst these studied compounds, thioureas 6a, 6c, 6h, and 6i were better inhibitors against bacterium S. aureus with MIC values of 0.78−3.125 μg/mL. These compounds were also tested for their inhibitions against S. aureus enzymes, including enzymes of DNA gyrase, DNA Topoisomerase IV (Topo IV), and Dihydrofolate reductase. Amongst these compounds, 6h was strong inhibitor with IC50 values of 1.22, 53.78, and 0.23, respectively. Induced fit docking calculations were performed to observe binding efficiency and steric interactions of these compounds. The obtained results showed that compound 6h was compatible with the active sites of S. aureus DNA Gyrase 2XCS. This ligand interacted with residues ASP1083 (chain D), MET1121 (chain B), ARG1122 (chain D) also with HOH2035, HOH2089, HOH2110, HOH2162. Molecular dynamics simulation in water solvent system showed that the active interactions with residues ASP083 and MET1121 (chain B) along with ASP1083, MET1121, and ARG1122 (chain D) played an important role in stabilizing complex 6h/2XCS in the active pocket.
Synthesis, biological and molecular modelling for 1,3,4-thiadiazole sulfonyl thioureas: Bacterial and fungal activity
