Two different thiosemicarbazone tauto-conformers coordinate to Palladium (II): Stability and biological studies of the final complexes

Abstract

Thiosemicarbazone moiety is a valuable scaffold for the synthesis of metallic complexes with anticancer purposes, when bearing N-heterocyclic the final compounds possess diverse biological activities. Using thiazole as bioisosteres, the resulting thiosemicarbazones can afford synthetic drugs with a variety of pharmacological effects. Trying to elucidate, if metal complexes from α-N-heterocyclic thiosemicarbazones can achieve more selectivity versus special tumor lines, we have developed new metal complexes with 1H imidazole-4-carboxaldehyde 4 N-ptolyl- and 4 N-phenylthiosemicarbazone (HL1 and HL2 respectively). The solution studies of these ligands showed a tautomeric equilibria in solution and their reaction with Li2PdCl4 proved the stability of both forms affording two mononuclear Pd(II) complexes. Both tautomeric forms are clearly coordinated to palladium center acting as two different bidentate ligands. Palladium complexes’ stability in biological buffers was investigated to stablish the optimal conditions for the evaluation of cytotoxicity, that on the triple negative adenocarcinoma cell line showed IC50 values in the low micromolar range. Complexes were also studied with CT DNA (UV-Visible spectroscopy and viscosity) and with the pBR322 plasmid supercoiled models, indicating non covalent interaction.