3,5-Diacetyl-1,2,4-triazol bis(4N-substituted thiosemicarbazone) palladium(II) complexes: Synthesis, structure, antiproliferative activity and low toxicity on normal kidney cells

Treatment of 4N-monosubstituted bis(thiosemicarbazone) ligands of 3,5-diacetyl-1,2,4-triazol series with lithium tetrachloridopalladate gave the dinuclear complexes of general formula [Pd(μ-H3L1–5)]2, but using dichloridobistriphenylphosphinepalladium(II) salt, the first mononuclear bis(thiosemicarbazone)–palladium–triphenylphosphine complexes of the 3,5-diacetyl-1,2,4-triazol series, [Pd(H3L1–5)PPh3], have been obtained. All the compounds have been characterized by elemental analysis and by IR and NMR spectroscopy, and the crystal and molecular structures of dinuclear complexes [Pd(μ-H3L3)]2 and [Pd(μ-H3L5)]2 as well as mononuclear complexes [Pd(H3L1)PPh3], [Pd(H3L2)PPh3], [Pd(H3L3)PPh3] and [Pd(H3L4)PPh3] have been determined by X-ray crystallography. The new compounds synthesized have been evaluated for antiproliferative activity in vitro against NCI-H460, A2780 and A2780cisR human cancer cell lines. Subsequent toxicity study, on normal renal LLC-PK1 cells, shows that all compounds investigated exhibit very low toxicity on kidney cells with respect to cisplatin.

Graphical abstractNew mononuclear and dinuclear palladium(II) complexes derived from N4-substituted bis(thiosemicarbazone) ligands have been synthesized and characterized. They exhibit important antitumour activity since they are capable of circumvent cisplatin resistance in A2780cisR cells and reducing toxicity on normal kidney cells.Figure optionsDownload full-size imageDownload as PowerPoint slide