Molecular Docking of Natural Phenolic Compounds for the Screening of Urease Inhibitors

Abstract

Background: Bacterial ureases have been the cause of various human and animal pathogenicity including hepatic encephalopathy, hepatic coma urolithiasis, gastric and peptic ulcers, pyelonephritis, and urinary catheter encrustation by the production of ammonia. Hence, in view of the side effects of existing drugs, there is a strong need to discover, more safe, effective and potent compounds for the treatment of infections caused by urease.

Methods: For this purpose, several natural phenolic compounds have been screened by molecular modelling techniques, wherein the phenolic compounds were docked to the active site of Jack bean urease (PDB ID 3LA4) using the Schrodinger docking software.

Results: The lead compounds were identified via in-silico screening technique where docking score, binding energy, ADME and toxicity data were considered to screen the lead compounds as compared with the available standard drugs. From the docking study of screened natural phenolic compounds, five compounds diosmin, morin, chlorogenic acid, capsaicin and resveratrol were selected based upon their better affinity towards the receptor and were considered for further wet lab studies.

Conclusion: The in-silico results were confirmed by in vitro experiments by use of the Jack bean urease using Weatherburn method.

Keywords: Gastric ulcer; Helicobacter pylori; chlorogenic acid; diosmin; docking; morin; urease..