Synthesis, structural characterization, in vitro and in vivo antitumor activities of Pt(II) complexes with di(pyridin-2-yl)methanone − hydrazone derivatives

Six Pt(II) complexes bearing di(pyridin-2-yl)methanone hydrazone derivative ligands ( Pt1 − Pt6 ) were synthesized and characterized. These complexes exhibited promising antiproliferative activity against multiple cancer cell lines, with low cytotoxicity toward normal human cells. Among them, Pt4 and Pt6 demonstrated the strongest inhibition of A2780 cell proliferation. Mechanistic studies revealed that Pt4 and Pt6 induce apoptosis via mitochondrial dysfunction, accumulation of intracellular Ca 2+ and reactive oxygen species, and activation of caspase-3/9. Importantly, Pt4 , the most potent agent against A2780 cells, displayed superior antitumor efficacy compared to cisplatin in an A2780 xenograft model, with no significant systemic toxicity.