Synthesis, Characterization, Antimicrobial Activity, Docking, and In Silico ADMET Analysis of Some New...

A series of 2,3-dihydrobenzo[b][1,4]thiazepine derivatives have been synthesized and characterized using IR, NMR, GC-MS and microanalysis. The compounds were found to exhibit variable activity against Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis and Salmonella typhi with MIC values ranging from 1.88-15 mg/mL. The best activity was observed in compounds 4 and 6 with MIC of 1.875 mg/mL against E. faecalis. Compound 6 was also the most active against S. aureus with MIC of 1.875 mg/mL. The in silico computational docking revealed that the compounds have excellent binding to both multiple targets of E. coli and Staphylococcus aureus dihydrofolate reductase enzymes (PDB ID: 6XG5 and 6P9Z) and good binding to the S. aureus dihydropteroate synthase enzyme (PDB ID: 1ad4). The computational pharmacokinetic study showed that the highly orally bioavailable compounds were not P-gp (p-glycoprotein substrate). The compounds were found to be excellent hERG blockers.