Palladium(II) and platinum(II) bis(thiosemicarbazone) complexes of the 2,6-diacetylpyridine series with high cytotoxic activity in cisplatin resistant A2780cisR tumor cells and reduced toxicity

Preparation and characterization of four novel 2,6-diacetylpyridine bis(N-4-tolylthiosemicarbazonato) palladium(II) and platinum(II) complexes, [PdL1-2] and [PtL1-2], are described. All compounds have been characterized by elemental analysis and by IR and NMR spectroscopy, and the crystal and molecular structures of complexes [PdL2] and [PtL2] have been determined by a single crystal X-ray diffraction. The ligands act as dianionic tetradentate donors coordinating to the metal center in a square planar geometry through the N-pyridinic atom and the N-iminic and the S atoms from one thiosemicarbazone arm, the fourth coordination position is occupied by the N-hydrazinic of the other arm. The new compounds synthesized have been evaluated for antiproliferative activity in vitro against NCI-H460, HepG2, MCF-7, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that [PdL1], [PdL2] and [PtL2] may be endowed with important antitumor properties since they are capable of not only circumventing cisplatin resistance in A2780cisR cells but also exhibiting high antiproliferative activity in breast cancer MCF-7 cells. Subsequent toxicity study, in LLC-PK1 cells, has also been carried out and shows that none of these compounds are in vitro toxic in the tested concentration range. (c) 2013 Elsevier Inc. All rights reserved.