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

• 2,6-Diacetylpyridine bis(4N-tolylthiosemicarbazonate) palladium(II) and platinum(II) complexes
• These complexes exhibit high cytotoxic activity in MCF-7 tumor cells and moreover are able to circumvent cisplatin resistance in A2780cisR cells.
• All complexes are in vitro non-toxic against normal LLC-PK1 renal cells at the concentration range tested.

Preparation 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 [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 Npyridinic 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 range.

Palladium and platinum bis(thiosemicarbazone) complexes of the 2,6-diacetylpyridine series have been synthesized and characterized. This study has identified the [PdL1], [PdL2] and [PtL2] complexes as having important antitumor activity since they are capable of circumventing cisplatin resistance in A2780cisR cells and reducing nephrotoxicity.Figure optionsDownload as PowerPoint slide