An Efficient Route for the Synthesis of 1,5-Disubstituted Tetrazoles and their Anti-Microbial Activity Against Salmonella Paratyphi

Carbimidothioates were synthesized by the reaction of Grignard reagents with arylisothiocyanates followed by methylation with methyl iodide. Further, these carbimidothioates were cyclized with sodium azide in DMF at 120 °C to get 1,5-disubstituted tetrazoles, which are important class of compounds in medicinal chemistry. Hence, we evaluated the antibacterial activity against Salmonella Paratyphi bacteria. Among the series, compounds 6 a, 6 c, 6 f and 6 i effectively inhibited Solamonella Paratyphi. Compound 6 f performed well in the agar well diffusion experiment. Compound 6 i outperformed the standard drug in micro dilution assay and biofilm inhibition experiment using Crystal violet at 1 mM concentration. These studies demonstrates that active molecules are the most promising options for reducing S. paratyphi biofilm. In order to know the binding mode of the synthesized molecules, we performed molecular docking studies with protein Salmonella Paratyphi A lipopolysaccharide acetyltransferase periplasmic domain (PDB ID-6SE1). Among the series, compounds 6 f and 6 i exhibited the most significant affinity score with 6SE1 protein