In vitro and in vivo studies on antitumor potential of Ni(II) and Pd(II) complexes based on a series of thiourea-based ligands

Palladium (II) complexes have been investigated as prospective chemotherapeutic agents for cancer treatment. This study aims to synthesize and characterize three thiourea-based ligands with different substituents (-H (ThU1), -Cl (ThU2), –CH₃ (ThU3)) and their corresponding Ni(II) and Pd(II) complexes. The synthesized ligands and metal complexes are well characterized by FT-IR, NMR, ESI-MS, and SC-XRD studies. SC-XRD analysis of PdThU1 and PdThU2 confirmed square planar geometries around the palladium centre. The in-vitro antiproliferative activities of ligands and metal complexes against a metastatic and highly aggressive metastatic murine lymphoma (DL) and human B cell lymphoma (Raji) cancer cells suggest Pd(II) complexes have a much better cytotoxic response than thiourea ligands and Ni(II) complexes. Interestingly, Pd(II) complexes PdThU1 (2.45 μM & 5.19 μM) and PdThU2 (4.7 μM & 9.54 μM) showed significantly lower IC₅₀ values compared to cisplatin (34.96 & 71.13 μM) against DL and Raji cancer cells, respectively. Further, direct cytotoxicity was studied using LDH release assay. The cell vialibity analysis of PdThU1 and PdThU2 against normal human lymphocytes and monocytes suggests their biocompatibility. Apoptosis induction was assessed using Annexin V-FITC/PI labelling and flow cytometry. In vivo investigations were performed on a BALB/c mouse DL tumour model to assess treatment effectiveness and biosafety. In vivo studies demonstrated that PdThU1 and PdThU2 significantly reduced tumour growth and prolonged survival, with minimal toxicity. Our data suggests that the Pd(II) complexes demonstrated significant antitumor effect against murine lymphoma both in vitro and in vivo.