Investigation of a set of flavonoid compounds as Helicobacter pylori urease inhibitors: insights from in silico studies

Helicobacter pylori (H. pylori) is a spiral, microaerophilic gram-negative bacterium, which is associated with the destruction of the lining of the stomach, leads to chronic inflammation of the stomach, which can cause stomach and duodenal ulcers. The problems caused by the treatment with antibiotics have caused researchers to use new approaches to treat infections caused by H. pylori, among them specific treatments with flavonoids. Urease enzyme, as one of the most important pathogenic and antigenic factors of this bacterium, is a suitable target for this purpose. In this study, the inhibitory effect of flavonoid compounds compared to acetohydroxamic acid on H. pylori urease enzyme was evaluated using molecular modeling methods. First, the interaction of flavonoids with urease enzyme compared with acetohydroxamic acid was investigated by molecular docking method to produce efficient docking poses. Then the physicochemical properties and toxicity of the best flavonoid compounds were analyzed using the swissadme server. Also, molecular dynamics calculations were performed to precisely understand the interactions between ligands and protein. The results of this study show that all the investigated flavonoid compounds are capable of inhibiting H. pylori urease. Among these compounds, six compounds chrysin, galangin, kaempferol, luteolin, morin and quercetin showed a greater tendency to bind to urease, compared to the acetohydroxamic acid inhibitor. These compounds are desirable in terms of physicochemical properties. This study also revealed that the flavonoids with their hydroxyl groups (-OH) play an important role during bond formation with amino acids Ala278, Ala169, His314, Asp362 and Asn168. Therefore, flavonoid compounds, due to their suitable location in the active site of the urease, create a more effective inhibition than the chemical drug acetohydroxamic acid and can be suitable candidates for the treatment of Helicobacter pylori under in vitro and in vivo investigations.