Rational Design, Synthesis, and Docking Simulation of Novel Derivative as Potent Urease Inhibitor

Ureases are nickel-dependent amidohydrolases(EC.۳.۵.۱.۵)that catalyze the hydrolysis of urea to form ammonia and carbamate. Urease occurs throughout the animal and plant kingdoms. Helicobacter pylori infection is associated with upper gastrointestinal diseases such as peptic and duodenal ulcers and gastric cancer development. Urease is the most characteristic feature of H. pylori and lacking urease activity is incapable of causing infection in animal models.Though consisting of inconsistent subunits ureases of different origins possess similar amino acid sequences and structures of the active site consequently sharing a common catalytic mechanism.Inhibition potentials of the same substances were noted to differ for ureases of various origins; however a general correlation is possible for microbial and plant enzymes.Experimental:In the urease inhibitory assay۱۰۰µl urease enzyme ۳۰µl of test compound at different concentrations and ۱۰۰µl urea were incubated at ۳۷ °C for ۱۵min after was added Berthelot(phenol-hypochlorite)reagent and further incubated at ۳۷ °C for ۳۰min. The IC۵۰ value of the test compound was calculated using GraphPad PRISM ۹.۰ software. The three-dimensional structure of urease (PDB ID: IE۹Y) was used for docking studies. The compound structure is optimized by ChemBio۳D ۱۷.۳. Computational docking experiments were carried out using AutoDock Vina v.۱.۱.۲.Results and discussion:The soybean Urease enzyme was used to test the inhibitory potential of the synthesized compound and it was the resultant IC۵۰=۳۷μM value that the synthesized compound showed inhibitory potential against the urease enzyme relative to that of the standard.The enzyme-ligand complex C۲۱H۱۵N۵O۶ shows the binding affinity energy -۸ kcal/mol to interact with the enzyme involved in hydrogen bond interaction. Conclusion:In the past decade the problem of urease inhibition has become important to medical practice. Molecular docking simulation is one of the most frequently used methods in Structure-Based Drug Design. looking for specific inhibitors in this study could suggest new potential drug candidates for such a common disease