Multimodal anticancer potential of newly synthesized palladium(II), platinum(II), and gold(III) complexes with...

Novel palladium(II), platinum(II), and gold(III) complexes, [PdCl₂(py-2tz)] (1), [PtCl₂(py-2tz)] (2), and [AuCl₂(py-2tz)][AuCl₄] (3), py-2tz is 2-(Thiazol-2-yl)pyridine-4,5-dicarboxylate dimethyl ester, were synthesized and characterized using spectroscopy (¹H and ¹³C NMR, IR, and UV-Vis), mass spectrometry, density functional theory (DFT), electrochemical (cyclic voltammetry), and crystallographic methods. Single-crystal X-ray diffraction analysis revealed that all complexes are square-planar with bidentate coordination of the py-2tz ligand via its pyridine and thiazole nitrogen atoms to the corresponding metal ion. These complexes were further evaluated against three human cell lines, two cancer (colon, HCT-116, and cervical adenocarcinoma, HeLa) and one healthy (embryonic lung fibroblast, MRC-5), using the MTT cytotoxicity assay. The influence of these complexes on the type of cell death and cell cycle progression were examined by flow cytometry. Of all the complexes investigated, the gold(III) complex showed the most prominent cytotoxicity toward tumor cells, with reduced toxicity against MRC-5 compared to cisplatin. Furthermore, this complex induced apoptosis and autophagy in both tumor cell lines, and G2/M arrest in HCT-116 cells. The binding interactions of the complexes 1-3 with bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) were also investigated using fluorescence spectroscopy, complemented by molecular docking simulations.