In-Silico Study of Urea Derivatives as a Potential DNA-Gyrase Inhibitors in Salmonella typhi

Salmonella Typhi is the infectious agent that causes typhoid fever. Among this disease's clinical symptoms are elevated body fever, headache, indigestion, body aches, fatigue, and cough. Salmonella Typhi is a pathogenic, rod-shaped, flagellated, and Gram-negative bacterium that causes typhoid fever. The objective of the present study was to investigate the inhibition potential of urea derivatives (Sorafenib and Regorafenib derivatives) against DNA-gyrase. In-silico molecular docking studies was used to explore the ligand-protein binding interaction of urea derivatives with DNA-gyrase. Autodock tools was used to prepare protein by removing water molecules and hetro-atoms and then started docking. Pymol and Discovery studio was used for visualization of the bonding interaction between ligand and protein. The research study shows that Sorafenib and its related designed compounds S1-S6 binding energy lies between (-11.27 to -13.79 kcal/mol) and Regorafenib its related designed compounds R1-R6 binding energy lies between (-12.66 to -15.01 kcal/mol) and have showed high potential against DNA-gyrase in Salmonella Typhi. Moreover, the designed derivatives have shown more inhibition potential then the standard drugs except S3 which have shown inhibition potential less than the standard drug. Overall results in this study indicates that the inhibitory potential of urea derivatives against DNA-gyrase in Salmonella Typhi are very good. Docking revealed strong hydrogen‑bonding interactions, notably with TYR‑835 and ARG‑120, suggesting the high inhibitory potential of these derivatives.These findings suggest that the urea derivatives have significant inhibitory potential against against DNA-gyrase in Salmonella Typhi and could serve as promising lead compounds for future in vitro and in vivo studies aimed at developing new anti-Typhid therapies