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

NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Inorganic Biochemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in JOURNAL OF INORGANIC BIOCHEMISTRY 125 (2013): 26-31 DOI http://dx.doi.org/10.1016/j.jinorgbio.2013.04.005Preparation and characterization of four novel 2,6-diacetylpyridine bis(4N-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 [PdL 2] 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 Niminic and the S atoms from one thiosemicarbazone arm, the fourth coordination position is occupied by the Nhydrazinic 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 rangeWe are grateful to Ministerio de Economía y Competitividad, Instituto de Salud Carlos III of Spain (PI080525 and PI1100659) for financial suppor