Síntese, caracterização e avaliação de complexos de paládio contendo chalconas sobre células de adenocarcinoma gástrico e Helicobacter pylori

Abstract

Chalcones are a class of α,β-unsaturated compounds widely recognized for their pharmacological potential, particularly due to their antitumor and antibacterial activities associated with a conjugated structure capable of interacting with diverse biomolecules and modulating biological processes. Coordination with transition metals such as palladium(II) has proven to be an effective strategy to enhance bioactive properties by modifying electronic, lipophilic, and structural characteristics. Considering the high incidence of gastric cancer and its close association with H. pylori infection, in this study, eight palladium(II) complexes containing chalcone-derived ligands were synthesized and characterized, aiming to evaluate their structural, spectroscopic, and biological properties against human gastric adenocarcinoma (AGS) cells, murine fibroblasts (L-929), H. pylori, and the urease enzyme. The structures were characterized by FTIR, UV-Vis, ¹H NMR, mass spectrometry, thermogravimetric, and elemental analyses. In in vitro assays, an increase in cytotoxicity against the AGS cell line was observed, reducing IC₅₀ values from 28–64 µM (ligands) to 6–26 µM (complexes). Complex 9C was the most active and selective (IC₅₀ = 6.38 µM; SI = 4), surpassing even cisplatin (IC₅₀ = 8.42 µM). Docking studies against the Bcl-2 protein showed interactions with critical residues in the active site, consistent with an intrinsic apoptotic mechanism. In the antibacterial evaluation, all complexes exhibited higher activity than the free ligands, with MIC = 1–4 µg/mL and MBC = 1–8 µg/mL. Complex 9C displayed the best profile (MIC and MBC = 1 µg/mL), followed by 14C and 12C, whose variations reflect electronic and lipophilic effects. In urease inhibition assays, only the metal complexes were active (IC₅₀ = 9.72–33.29 µM), suggesting that Pd(II) may compete with Ni²⁺ at the catalytic site, thereby reducing enzymatic function. Overall, the results demonstrate that metal coordination significantly enhances the biological activity of chalcones, conferring integrated antitumor and anti-H. pylori potential. Structural variations in the cores and substituents modulate selectivity and potency, highlighting complexes 7C, 9C, and 14C as promising candidates for the development of new compounds targeting gastric cancer and H. pylori-associated infections.