Metabolic alterations are increasingly recognized as important aspects of colorectal cancer (CRC), offering potential avenues for identifying therapeutic targets. Previous studies have demonstrated the cytotoxic potential of bamboo leaf extract obtained from Guadua incana (BLEGI) against HCT-116 colon cancer cells. However, the altered metabolic pathways in these tumor cells remain unknown. Therefore, this study aimed to employ an untargeted metabolomic approach to reveal the metabolic alterations of the endometabolome and exometabolome of HCT-116 cells upon exposure to BLEGI treatment. First, a chemical characterization of the BLEGI was conducted through liquid chromatography coupled with mass spectrometry (LC-MS). Next, we assessed cell viability via MTT and morphological analysis using an immunofluorescence assay against colon cancer cells, and anti-inflammatory activity using an LPS-stimulated macrophage model. Subsequently, we employed LC-MS and proton nuclear magnetic resonance (¹H-NMR) to investigate intra- and extracellular changes. Chemical characterization primarily revealed the presence of compounds with a flavone glycoside scaffold. Immunofluorescence analysis showed condensed chromatin and subsequent formation of apoptotic bodies, suggesting cell death by apoptosis. The results of the metabolomic analysis showed 98 differential metabolites, involved in glutathione, tricarboxylic acid cycle, and lipoic acid metabolism, among others. Additionally, BLEGI demonstrated significant nitric oxide (NO) inhibitory capacity in macrophage cells. This study enhances our understanding of BLEGI’s possible mechanism of action and provides fresh insights into therapeutic targets for treating this disease.

Aims: We synthetized 10 hydroxylated and methoxylated chalcones and evaluated them targeting MMP-9 inhibition, looking for the rate of adhesion of H. pylori in gastric cells, and then, reduction of the inflammatory response as alternative therapeutic agents for controlling the infection. Background: Helicobacter pylori is a Gram-negative bacterium that chronically infects the human stomach, a risk factor for the development of inflammatory gastrointestinal diseases, including cancer, and is classified as a group I carcinogen. It is estimated that it infects around 45% of the global population and that the persistence of the infection is related to the adhesion of the bacteria in the gastric epithelium. The progression of gastric lesions to cancer is connected to the activation of the NF-κB and MAPK pathways, especially in cagA+ strains, which are related to increased expression of MMP-9. The activation of these metalloproteinases (MMPs) contributes to the adhesion of the bacterium in gastric cells and the evolving stages of cancer, such as enabling metastasis. Due to the increasing resistance to the current therapy protocols, the search for alternative targets and candidate molecules is necessary. In this way, controlling adhesion seems to be a suitable option since it is a crucial step in the installation of the bacterium in the gastric environment. Objective: Synthetize ten hydroxylated and methoxylated chalcones. Assess their anti-H. pylori potential, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). Evaluate their cytotoxicity in AGS cells and selectivity with L-929 cells. Analyze the results and correlate them with in silico predictions to evaluate potential anti-adhesive properties for the chalcones against H. pylori. Method: The chalcones were synthetized by Claisen-Schmidt condensation using Ba(OH)₂ or LiOH as catalysts. Predictive in silico assays in PASS Online, tanimoto similarity, ADME properties and molecular docking in MMP-9 (PDB code: 6ESM) were performed. The in vitro assays carried out were the cell viability in gastric adenocarcinoma cells (AGS) and fibroblasts (L-929) by the MMT method and anti-H. pylori, by the broth microdilution method, through the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results: Ten chalcones were synthesized through Claisen-Schimdt condensation with yields of 10 to 52% and characterized by ¹H and ¹³C nuclear magnetic resonance (NMR) and mass spectrometry (MS). in silico data revealed the possibility of anti-H. pylori, anti-inflammatory, and MMP-9 inhibition for the chalcones. Chalcone 9 showed the best growth inhibition values for MIC and MBC, at 1 μg/mL and 2 μg/mL, respectively. Chalcones 14 and 15 likewise demonstrated excellent inhibitory results, being 2 μg/mL for both MIC and MBC. Additionally, 15 had the best MMP-9 inhibition score. Despite not corroborating the in silico findings, chalcones 10, 13, and 18 showed good cytotoxicity and the best selectivity indices. Conclusion: All compounds exhibited strong activity against H. pylori, specially 15. The predicted MMP-9 inhibition by molecular docking added to the reasonable SI and CI₅₀ values for 15 and the satisfactory reduction in the rate of survival of the bacteria, reveals that it may be acting synergically to reduce the inflammatory response and the possibilities for developing a tumor by inhibiting both bacteria and malignant cells.

Medicinal plants and their phytocompounds are valuable shortcuts for discovering new, safer biologically active compounds or herbal medicines with reduced adverse effects. In this study, medicinal plant species were initially selected from Brazilian traditional medicine using a database of in silico and in vitro studies. A virtual screening study was carried out with a phytochemical database previously reported in the literature. The biological activity was evaluated in silico by PASS Online and molecular docking, then validated by in vitro anti-Helicobacter pylori assay. The chemical profile of the species was obtained by ESI(±)FT-ICR MS and LC-MS-DAD analysis. Vernonia condensata, Bauhinia forficata, Jatropha gossypiifolia, and Sonalum paniculatum were selected based on a survey of the literature for use of gastric diseases and anti-Helicobacter pylori potential. After PASS analysis, Jatropha gossypiifolia was selected for in vitro study because its compounds showed anti-H. pylori activity potential, inhibiting fumarate reductase enzyme. J. gossypiifolia extracted showed MIC of 64 µg/mL and MBC of 128 µg/mL in the in vitro anti-H. pylori assay. ESI(±)FT-ICR MS and LC-MS-DAD analysis showed compounds such as luteolin (1), isovitexin (2), luteolin-7-O-glucoside (3), isoorientin (4), and 3-genistein-8-C-glucoside (5). Molecular docking analysis showed a potential interaction of compounds in the enzyme active site such as hydrogen bonds with Arg404 and a similar interaction to fumaric acid, except for isoorientin (4). J. gossypiifolia showed promising activity and may represent a future alternative to treat H. pylori infections and their deleterious effects, reinforcing the therapeutic potential of this plant.

Colorectal cancer is one of the most prevalent malignancies worldwide, with the global incidence projected to reach approximately 3.2 million cases by 2040. Mesoporous silica nanoparticles have been extensively investigated as promising drug delivery systems for cancer therapy. Chalcones, key precursors of flavonoids, have demonstrated notable cytotoxic activity, and structural modifications involving diverse functional groups have been shown to further enhance their antitumor efficacy. Within this context, we evaluated a synthetic chalcone against colorectal cancer cells (HCT-116) using the MTT tetrazolium assay. The 2′-hydroxy-2-fluorochalcone was incorporated into MCM-41 (Mobil Composition of Matter No. 41) and into matrices functionalized with 3-aminopropyltriethoxysilane (APTES) and folic acid. The nanoparticles were synthesized and characterized by thermogravimetric analysis (TGA), elemental analysis (CHN), scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta potential, and nitrogen adsorption. Evaluate its cytotoxicity in HCT-116 cells and selectivity (IS) with L-929 cells. Molecular docking showed interactions between amino acid residues and functional groups of 2′-hydroxy-2-fluorochalcone that was very important to its cytotoxicity and activity about proteins: thymidylate synthase and vascular endothelial growth factor receptor 2 (VEGFR2). In vitro release assay was carried out to verify the release profile of the chalcone from the nanoparticles. In vitro cytotoxic tests showed that the MCM-APTES-AF-CH sample improved the IC ₅₀ [IC ₅₀ of 2.73 ± 0.96 μM (IS: 5.66)] against the HCT-116 cells. Hemolysis assay showed that the samples did not cause hemolysis in the concentrations tested. These findings indicate that MCM-APTES-AF-CH represents a promising nanocarrier platform for enhancing the anticancer efficacy of novel chalcone derivatives against colorectal cancer cells.

Introdução: O uso de nanocarreadores tem sido cada vez mais estudado como opção terapêutica no tratamento de neoplasias. Esses nanomateriais podem transportar agentes antineoplásicos para tecidos afetados por células cancerígenas e liberá-los controladamente, evitando efeitos citotóxicos em células saudáveis. Dentre uma gama de nanocarreadores, a nanopartícula de sílica mesoporosa é uma das mais exploradas nessa área. Uma molécula bioativa que vem sendo amplamente estudada devido a um potencial antitumoral é a chalcona. Objetivos: Avaliar o grau de incorporação e liberação da molécula de chalcona em nanopartículas de sílica mesoporosa. Material e Método: Para realizar a síntese de nanopartículas de MCM-41, o surfactante brometo de cetiltrimetilamônio (CTAB) foi dissolvido em água e misturado com NaOH também dissolvido. A mistura foi posta em banho-maria, no qual tetraetilortossilicato (TEOS) foi gotejado quando a temperatura se estabilizou a 80°C. Posteriormente, realizou-se centrifugação, lavagem, secagem e calcinação a 550°C, obtendo-se um pó branco como produto final. Foi utilizada microscopia eletrônica de varredura (MEV) para caracterizar a morfologia da superfície da MCM-41. Para o método de incorporação, as nanopartículas de MCM-41 foram deixadas em contato com a solução de hidroxichalcona 2000μg/ml, tendo o butanol como solvente, durante 48 horas. A liberação foi quantificada utilizando espectrofotômetro UV-Vis. Uma curva de calibração foi preparada para a quantificação. Resultados: As imagens obtidas por MEV indicaram nanopartículas com formato predominantemente esférico e distribuição homogênea de tamanho. A hidroxichalcona apresentou comprimento de onda de 308nm, gerando a equação da reta de y=0,0668x-0,003 com R²=0,9995. A incorporação do fármaco na nanopartícula foi de 12,25% e a porcentagem média de fármaco liberado, determinado em triplicata, foi de 5,76% após 48 horas. Discussão : O R² da curva de calibração indica uma boa correlação entre os dados. Os valores de incorporação se demonstraram satisfatórios e a porcentagem da biomolécula liberada, após as 48 horas, indica um potencial de liberação controlada ao decorrer do tempo. Conclusão: Dados os resultados apresentados, foi possível realizar o processo de síntese de MCM-41, incorporação e liberação do fármaco com sucesso, indicando a possibilidade de criação de um sistema de liberação de fármaco controlado para futuras aplicações terapêuticas.