Synthesis, structural characterization, and antitumor evaluation of Pd(II) Thiosemicarbazide–Diphosphine complexes in 2D and 3D cancer models

P NMR, high-resolution mass spectrometry, UV-Vis spectroscopy, and single-crystal X-ray diffraction. The structural analyses confirmed distorted square-planar Pd(II) geometries featuring N,S-bidentate thiosemicarbazide and chelating bisphosphine ligands. The cytotoxicity of the complexes was evaluated against breast (MCF-7 and MDA-MB-231), prostate (DU-145), lung (A549), ovarian (A2780 and A2780cis), and non-tumor (MRC-5) cell lines using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. One of the complexes exhibited the highest cytotoxicity, with IC₅₀ values approaching 1 μM in ovarian and breast cancer cells. B3 was about 25-30 times more active and selective than cisplatin (SI ≈ 15). Additional tests demonstrated that B3 blocked colony formation and migration, triggered dose-dependent apoptosis, and exhibited minimal toxicity to non-tumor cells. Notably, B3 demonstrated significant activity against cisplatin-resistant ovarian cells (A2780cis) in three-dimensional (3D) spheroid cultures, indicating its potential under physiologically relevant conditions. Overall, the structural features represent a promising lead compound for developing next-generation palladium-based metallodrugs with improved selectivity and effectiveness against resistant tumor types.