Chemistry, antiproliferative activity and low nephrotoxicity of 3,5-diacetyl-1,2,4-triazol bis(4N-thiosemicarbazone) ligands and their platinum(ii) complexes

Abstract

The preparation and characterization of 3,5-diacetyl-1,2,4-triazol bis(4,4-dimethylthiosemicarbazone) ligand, H₃L¹, and its dinuclear platinum complex [Pt(μ-HL¹)]₂ is described. The crystal and molecular structure of the platinum complex has been resolved by single crystal X-ray diffraction. The ligands coordinate, in an asymmetric dideprotonate form, to the platinum ions in a tridentate fashion (NNS) and S-bridging bonding modes. Thus the molecular units of the platinum complexes are stacked as dimers. The new compounds synthesized together with the analogous monosubstituted ligand 3,5-diacetyl-1,2,4-triazol bis(4-methylthiosemicarbazone) (H₅L²) and its dinuclear platinum(II) complex [Pt(μ-H₃L²)]₂ have been evaluated for antiproliferative activity in vitro against NCI-H460, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumor properties, especially H₃L¹ and [Pt(μ-H₃L²)]₂ since they not only circumvent cisplatin resistance in A2780cisR cells but also exhibit high antiproliferative activity in human non-small cell lung cancer NCI-H460 cells. Subsequent nephrotoxic study, in LLC-PK1 cells, show that the four compounds investigated exhibit very low nephrotoxicity with respect to cisplatin.