Synthesis, structural characterisation, and anticancer potential of mono and dinuclear Pd(ii) complexes of N-(2-pyridyl)thiourea

Abstract

Cancer is a prominent global cause of mortality. Palladium complexes have the potential to serve as effective anticancer and pharmacological agents, offering a viable alternative to platinum medications. This work focused on the development of a new thiolato-bridged dinuclear [Pd(M3MPyThU)Cl]₂ and mononuclear palladium [Pd(M3MPyThU)₂] complexes containing 1-methyl-3-(3-methylpyridin-2-yl) thiourea (HM3MPyThU) ligand. The prepared ligand and complexes have been fully characterised by various spectroscopic and single-crystal crystallographic data. The ligand and complexes were further examined for their anticancer activities against the HT-29 (human colon) and MCF-7 (human breast) cancer cells along with the standard drug cisplatin, and the outcome suggests that tested compounds have a better cytotoxic response against HT-29 cells. The order of anticancer activity was found as [Pd(M3MPyThU)Cl]₂ > cisplatin > [Pd(M3MPyThU)₂] > HM3MPyThU. The complex [Pd(M3MPyThU)Cl]₂ demonstrated potent cytotoxic effects against HT-29 cells with an IC₅₀ value of 10 ± 3.3 μM. The comparison of the anticancer activity of the described complexes with previous reports on HT-29 cells suggests that the described complexes have better anticancer activity than previously reported complexes. Further assays were performed for [Pd(M3MPyThU)Cl]₂ to gain insights into the mechanism of cell death and found that reduced mitochondrial membrane potential and increased ROS production, highlighting mitochondrial-dependent apoptosis as the major mechanism for tumour cell death. Additionally, [Pd(M3MPyThU)Cl]₂ was found to be more selective compared to cisplatin since it exhibited decreased toxicity towards healthy cells (HEK-293).