Estudos in vitro e in silico de chalconas com potencial anti-helicobacter pylori, anti-inflamatório e antitumoral

Abstract

Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa of 50% of the world population, being considered the main etiological agent of chronic gastritis and human peptic ulcer. H. pylori infection is also associated with gastric cancer, being associated with 75% of the cases. Considering the need for alternative treatments for H. pylori infection, in this study, the anti-H. pylori, anti-inflammatory, and antitumor activities were evaluated of a series of 14 chalcones obtained by organic synthesis. The anti H. pylori activity was evaluated by determining the minimum inhibitory concentration (MIC), minimum bactericide (CBM) and evaluating the inhibition of the urease enzyme. Evaluation of H. pylori’s morphology changes was performed using scanning electron microscopy (SEM). For anti-inflammatory activity, the inhibition of the nitric oxide (NO) production in LPS-stimulated macrophages was evaluated. The cytotoxic action on gastric adenocarcinoma (AGS) cells was also evaluated by MTT-tetrazolium method. In silico studies were carried out to evaluate the interaction potential of chalcones at urease and iNOS active sites and a search for antitumor target was performed. The most active chalcones showed MICs ranging from 8 to 64 µg/mL Regarding urease inhibition, no significant inhibitory activity of the samples and no favorable interactions in the active site of the enzyme were verified. Morphological changes in H. pylori were observed for the most active chalcones, suggesting a role in the Penicillin-Binding Proteins (PBPs). The samples inhibited the NO production in LPS-stimulated macrophages and demonstrated, in silico, the potential for interaction in the active site of the iNOS enzyme. In addition, chalcones have demonstrated significant cytotoxic activity on AGS cells (IC50 ranging from 1,07 to 47,95 µg/mL). The search for antitumor targets indicated a high probability of the evaluated chalcones to be active against caspase-3, specifically by Bcl-2 inhibition, being this activity evaluated by molecular docking. Thus, the results suggests that these chalcones have the potential to be used as candidates for new and effective drugs to control H. pylori and diseases associated to it.