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

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 105.12 (2011): 1613-1622 DOI http://dx.doi.org/10.1016/j.jinorgbio.2011.08.014Treatment 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-H 3L 1-5)] 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(H 3L 1-5)PPh 3], 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-H 3L 3)] 2 and [Pd(μ-H 3L 5)] 2 as well as mononuclear complexes [Pd(H 3L 1)PPh 3], [Pd(H 3L 2)PPh 3], [Pd(H 3L 3)PPh 3] and [Pd(H 3L 4)PPh 3] 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 cisplatinWe are grateful to Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (PI080525), Universidad Autónoma de Madrid and Comunidad de Madrid (CCG08-UAM/SAL-4000) of Spain for financial suppor