title: New bioactive 2,6-diacetylpyridine bis(p-chlorophenylthiosemicarbazone) ligand and its Pd(II) and Pt(II) complexes: synthesis, characterization, cytotoxic activity and DNA binding ability.
abstract: Preparation and characterization of 2,6-diacetylpyridine bis((4)N-p-chlorophenylthiosemicarbazone) ligand, H2L, and its palladium(II) and platinum(II) complexes [PdL] and [PtL], is described. The molecular structure of the two new complexes has been determined by single crystal X-ray diffraction. The ligand acts as dianionic tetradentate donor coordinating to the metal center in a square planar geometry through the pyridine nitrogen atom and the azomethine nitrogen and thione sulfur atoms from one thiosemicarbazone arm, the fourth coordination position is occupied by the hydrazine nitrogen atom of the other arm. New free ligand and its metal complexes have been evaluated for antiproliferative activity in vitro against NCI-H460, T-47D, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumor properties, especially H2L and [PtL] since they are capable of not only circumvent cisplatin resistance in A2780cisR cells but also exhibit high antiproliferative activity in breast cancer T-47D cells. The interaction of H2L with calf thymus DNA was also investigated and its binding constant (Kb) determined.
authors.affiliation: Departamento de Química Inorgánica (Módulo 07), Facultad de Ciencias, c/Francisco Tomás y Valiente no. 7, Universidad Autónoma de Madrid, 28049, Madrid, Spain. Electronic address: ana.matesanz@uam.es.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Matesanz
authors.affiliation: Departamento de Química Inorgánica (Módulo 07), Facultad de Ciencias, c/Francisco Tomás y Valiente no. 7, Universidad Autónoma de Madrid, 28049, Madrid, Spain; Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Ciencias del Medio Ambiente, Avd. Carlos III s/n, Universidad de Castilla-La Mancha, 45071, Toledo, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Hernández
authors.affiliation: Departamento de Química Inorgánica (Módulo 07), Facultad de Ciencias, c/Francisco Tomás y Valiente no. 7, Universidad Autónoma de Madrid, 28049, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Souza
mesh_terms: D045744:Cell Line, Tumor; D003460:Crystallization; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D010165:Palladium / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D010984:Platinum; D010165:Palladium; D012264:Ribonucleotide Reductases
keywords: 2,6-Diacetylpyridine; Antitumor activity; Asymmetric coordination; Palladium and platinum complexes; Thiosemicarbazone