Role of the auxiliary ligand in determining the genotoxicity and mode of cell death of thiosemicarbazone Pd() complexes

A series of Pd( ii ) complexes of the general formula [PdX(NNS)] (X = Cl, Br, I, NCS and phenyl-tetrazole-thiolato; NNS = 2-quinolinecarboxyaldehyde- N 4 -phenylthiosemicarbazone) was tested against four malignant cell lines for their antiproliferative properties and the outcomes were compared to those seen in normal mouse splenocytes. Various auxiliary ligands were substituted in order to investigate the impact of the character of the ligand on the cytotoxicity of this class of Pd( ii ) complexes. The iodo complex was the most cytotoxic compound towards the Caco-2 cell line in this study. The improved apoptosis and necrosis cell modes were in accordance with the fragmentation results of DNA, which revealed increased fragmentation terminals, especially in isothiocyanate and tetrazole-thiolato complexes. After 24 hours, at half the IC 50 of each complex, the complex-treated cells exhibited considerable genotoxicity when compared to the corresponding non-treated control especially in the case of isothiocyanate and tetrazole-thiolato complexes. We report how the cytotoxicity, mode of death and genotoxic effect of a series of square planar Pd( ii ) complexes are determined by the auxiliary ligand coupled to the Pd( ii ) ion, which is chelated by the tridentate thiosemicarbazone ligand.