Synthesis, Characterization, and Biological Evaluation of Noble Metal Complexes with 2-(1-Benzyl-1H-1,2,3-triazol-4-yl)pyridine Ligand: An Interesting Class of Metallo-antimicrobial and -antitumor Agents

The rise of antimicrobial resistance (AMR) and Multidrug Resistance (MDR) has compelled the scientific community to search for new families of antimicrobial agents. Coordination compounds of noble metals have been shown to be good candidates, not only as novel antimicrobials but also as antitumor drugs. Herein we report the synthesis of a series of palladium(II), platinum(II) and gold(III) chelated complexes with a triazole-pyridine ligand, 2-(1-benzyl-1H-1,2,3-triazol-4-yl)pyridine, 5-TzPy. The complexes were isolated and characterized in solution by means of NMR spectroscopy, and their antibacterial, antifungal, and cytotoxic activities were tested. Among them, cationic gold compound 5, [Au(5-TzPy)Cl2][BF4], exhibited the best overall antimicrobial and antibiofilm activity. It proved to be the most potent compound, showing the lowest MIC and MBC values, and the greatest efficacy against biofilm formation. These findings suggest that its ionic charge and chemical configuration enhance molecular diffusion and interaction with microbial cells. In addition, electrochemical data show a redox behavior for complex 5 which may be associated with an oxidative stress mechanism of action. Additionally, the study was extended to include preliminary assessments of antitumor activity. Cytotoxicity tests on human tumor (HT29) cells showed that complexes 3, [Pt(5-TzPy)Me2], and 5, [Au(5-TzPy)Cl2][BF4], exhibited the highest tumor cell toxicity. However, cytotoxicity studies on normal endothelial (EA.hy926) displayed a more favorable selectivity profile for complex 2, [Pt(5-TzPy)Cl2]. Its moderate toxicity toward tumor cells and minimal effects on normal cells highlight the potential of 2 as a selective and safer antitumor agent.