New palladium and platinum complexes with bioactive 3,5-diacetyl-1,2,4-triazol bis(4-cyclohexyl thiosemicarbazone) ligand: chemistry, antiproliferative activity and preliminary toxicity studies

Abstract

The preparation and characterization of the new 3,5-diacetyl-1,2,4-triazol bis(4-cyclohexyl thiosemicarbazone) ligand, H₅5L¹1, is described. Treatment of H₅5L¹1 with K₂PtCl₄ gave the dinuclear complex [Pt(H₃L¹)]₂, 1, but using MCl₂(PPh₃)₂ where M = Pd or Pt, mononuclear complexes 2 and 3, of general formula [M(H₃L¹)PPh₃], were obtained. Subsequent reaction of the [Pd(H₃L¹)PPh₃] complex with PdCl₂(PPh₃)₂ yielded a new dinuclear complex [(PPh₃)Pd(H₂L¹)PdCl], 4. All compounds have been characterized by elemental analysis and FAB⁺ spectrometry and by IR and NMR spectroscopy. The molecular structures of mononuclear complexes 2 and 3 and dinuclear complex 4 have been determined by X-ray crystallography. 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 the H₅5L¹1 ligand and [Pt(H₃L¹)]₂, complex 1, may be endowed with important cytotoxic properties since they are capable of not only circumventing cisplatin resistance in A2780cisR but also exhibit antiproliferative activity in NCI-H460. The interactions of these compounds with calf thymus DNA were investigated by UV-vis absorption and a nephrotoxic study, in LLC-PK1 cells, has also been carried out.