Synthesis, Characterization, and Evaluation of Palladium(II) Complexes Containing Chalcones on Gastric Adenocarcinoma...

Metal-chalcone complexes have emerged as promising scaffolds in bioinorganic medicinal chemistry; however, their potential as dual-acting agents targeting both gastric cancer and Helicobacter pylori infection remains insufficiently explored. In this study, eight palladium-(II) complexes containing chalcone-derived ligands were synthesized and characterized, corresponding to the molecular formulas C₃₀H₂₂Cl₄O₄Pd (1C), C₃₈H₂₄Cl₂O₄Pd (2C), C₃₈H₂₈Cl₂O₄Pd (3C), C₄₀H₃₀O₆Pd (4C), C₃₀H₂₄Cl₂O₄Pd (5C), C₃₀H₂₀F₂O₄Pd (6C), C₃₂H₂₆O₆Pd (7C), and C₃₈H₂₄F₂O₄Pd (8C). The complexes were evaluated for cytotoxic activity against human gastric adenocarcinoma cells (AGS), antibacterial activity against H. pylori, and inhibition of the urease enzyme. Structural characterization was carried out by using UV-vis and FTIR spectroscopy analyses, ¹H NMR spectroscopy, high-resolution mass spectrometry, elemental analysis, and thermogravimetric analysis. In cytotoxicity assays, most palladium-(II) complexes exhibited enhanced activity and selectivity compared to their corresponding free ligands, with selected derivatives, including complexes 1C, 4C, and 8C, showing improved selectivity indices relative to cisplatin. Against H. pylori, all complexes displayed bactericidal activity stronger than that of the free ligands, with naphthol-based derivatives bearing methoxy or fluorine substituents showing the highest activity. In urease inhibition assays, several complexes were active, with phenolic derivatives exhibiting more pronounced effects; among them, complex 5C showed the lowest IC₅₀ value (9.72 μM). Molecular docking studies were employed as a qualitative and exploratory tool to rationalize trends observed in the in vitro assays, revealing consistent interaction patterns between the most active complexes and key catalytic residues of urease, including binding geometries compatible with coordination to the Ni²⁺ ions at the active site. The results demonstrate that coordination to palladium-(II) significantly modulates the biological profile of chalcone ligands, enhancing both cytotoxic and antibacterial activities. These findings highlight palladium-chalcone complexes as promising lead structures for the development of multifunctional agents targeting gastric cancer and H. pylori-associated diseases.