Pd(II)–PPh₃ complexes of halogen substituted acylthiourea ligands: Biomolecular interactions and in vitro anti-proliferative activity

Herein, we report the synthesis of four new Pd(II) acylthiourea complexes (C1–C4) to study the effect of halogen substituted acylthiourea ligands on the biological applications of their Pd(II)–PPh₃ complexes. The complexes were characterized by various spectroscopic and analytical methods. The distorted square planar geometry of complexes was confirmed by single crystal X-ray diffraction study, which also revealed the bidentate (N, S) coordination of the ligands with Pd(II). Interactions of the complexes with biomolecules (DNA/BSA) were investigated by spectroscopic and docking tools. All the complexes showed good binding ability with the targeted biomolecules. Further, in vitro anti-proliferative activity of the complexes was investigated by performing MTT assay on cancer (HeLa-cervical, HCT116-colorectal, and HepG2-hepatic) and normal (HEK293-embryonic kidney) cell lines. All the complexes displayed remarkable activity on the three cancer cells, and among them, complex C2 bearing chlorine substituted acylthiourea showed superior activity on HeLa cells with an IC₅₀ value of 6.5 μM, which was higher than that of cisplatin. Apoptosis induced by C2 on HeLa cells was assessed by AO/EB, DAPI and DNA laddering assays, and flow cytometry. Finally, the apoptotic efficiency of C2 was tested by cell cycle analysis, wherein the complex induced the cell cycle arrest in HeLa cells at G0/G1 phase.