Jessica Raquel Borges Monteiro

Studies estimate that nearly 2 million new cases of gastric cancer will occur worldwide during the next two decades, which will increase mortality associated with cancer and the demand for new treatments. Marine algae of the Laurencia genus have secondary metabolites known for their cytotoxic action, such as terpenes and acetogenins. The species Laurencia obtusa has demonstrated cytotoxicity against many types of tumors in previous analyses. In this study, we determined the structure of terpenes, acetogenins, and one fatty acid of Laurencia using mass spectrometry (ESI-FT-ICR/MS). In vitro cytotoxicity assays were performed with adenocarcinoma gastric cells (AGS) to select the most cytotoxic fraction of the crude extract of L. obtusa. The Hex:AcOEt fraction was the most cytotoxic, with IC₅₀ 9.23 µg/mL. The selectivity index of 15.56 shows that the Hex:AcOEt fraction is selective to cancer cells. Compounds obtained from L. obtusa were tested by the analysis of crystallographic complexes. Molecular docking calculations on the active site of the HIF-2α protein showed the highest affinity for sesquiterpene chermesiterpenoid B, identified from HEX:AcOEt fraction, reaching a score of 65.9. The results indicate that L. obtusa presents potential compounds to be used in the treatment of neoplasms, such as gastric adenocarcinoma.

Helicobacter pylori is a bacterium that reaches half of the world population and it’s recognized as the main cause of chronic gastritis and peptic ulcer. In this study, we evaluated the anti-H. pylori, antioxidant and immunomodulatory activities of the methanolic (MeOH) extract of Eugenia uniflora leaves and chemical profile. Anti-H. pylori activity was evaluated by spectrophotometric broth microdilution technique by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), in addition to the evaluation of the effect on the urease enzyme. The antioxidant activity was evaluated by capturing O₂ ^•-, HOCl e NO^• radicals. The immunomodulatory effect was evaluated on the cytokines TNF-α, IL-6 and on nitric oxide through inhibition in LPS-stimulated macrophages. The chemical profile was performed by total phenolic, tannin and flavonoid contents and mass spectrometry analysis by ESI-FT-ICR MS. In the anti-H. pylori assay the extract showed MIC of 128 μg/mL, however it did not obtain MBC. The extract also showed ability to inhibit the urease enzyme about 20%. The antioxidant activity of the MeOH extract showed EC₅₀ values of 29.77 µg/mL, 15.71 µg/mL and 442.10 µg/mL to O₂ ^•-, HOCl and NO^•, respectively. The extract also showed influence on the release of TNF-α, IL-6 and NO in LPS-stimulated macrophages, ranging from 39% to 97% inhibition. Flavonoids, phenylpropanoids, tannins, triterpenoids and carbohydrates were the major classes of compounds present in the MeOH extract as identified by (-)-ESI-FT-ICR MS. The results indicate important anti-H. pylori, antioxidant and immunomodulatory activities from Eugenia uniflora highlighting its importance in the prevention and treatment of diseases caused by H. pylori infection.