Synthesis, Enzymatic Assay and Molecular Docking Studies of Biuret Derivatives for Discovery of New Urease Inhibitors as Potential Agents Against Helicobacter Pylori Infection

Helicobacter pylori is a gram-negative spiral bacterium that causes infections in the human stomach and isable to survive in the acidic environment of the stomach with the help of the enzyme urease. By convertingurea to ammonia and carbon dioxide, this enzyme modulates the pH and facilitates survive of H. pylori inthe stomach because of providing a neutral environment in acidic conditions. Therefore, the virulence of H.pylori could be controlled using substances that inhibit urease activity. Due to the structure of biurets , whichconsists of two ureases and is similar to the urease substrate, they can be considered as potential ureaseinhibitors. In this project, urease inhibitory activity of ۱۸ biuret derivatives that have already been synthesizedwas investigated by molecular docking studies and the best compounds were selected to evaluate theenzymatic assay.The crystal structure of Jack bean urease (PDB code:۳la۴) was obtained from Protein Data Bank(www.rcsb.org). After validation, biuret derivatives were investigated by docking studies. The selectedcompounds are the ones that have the lowest docking score. Finally, selected compounds were evaluated byenzymatic assay.

Keywords:

Synthesis , Molecular Docking , Biuret Derivatives , Inhibitor , Urease