Synthesis, structural elucidation, and anticancer mechanisms of Pd(II)-acylthiourea complex: An integrated experimental and theoretical investigation

We present the synthesis and characterization of a novel acylthiourea-based ligand and its corresponding Pd(II) complex. The structural features and coordination behavior of the ligand in the formation of the complex were characterized using FTIR, UV–vis, ¹H/¹³C NMR spectroscopy, single crystal X-ray diffraction (for the complex), and mass spectrometry. The Pd(II) complex crystallized in the triclinic crystal system with a P-1 space group, exhibiting a slightly distorted square-planar geometry as determined by single-crystal X-ray diffraction analysis. The anticancer activity of the compounds, including the ligand and its Pd(II) complex was evaluated against various cell lines (MCF7, MDA-MB-231, T24, HepG-2, and MCF-10a) and compared to standard chemotherapeutic agents, cisplatin and doxorubicin. The IC₅₀ values of the mononuclear Pd(II) complex demonstrated the most potent cytotoxic and antiproliferative effects, outperforming both the ligand and cisplatin across all tested cell lines. The mechanism of representative Pd(II) complex was studied using apoptosis assays, fluorescence (AO/EtBr), DAPI, PI assays, JC-1 staining, mitochondrial membrane potential (ΔΨ_m), and reactive oxygen species (ROS) analysis, illustrating that this compound could induce apoptosis in MCF7 cells. Additionally, computational studies, including docking and ADMET, were performed to optimize structures and pharmacokinetic properties. The optimized structures were used to interact with EGFR tyrosine kinase and human folate receptor alpha using molecular docking.