Palladium(II) complexes with thiosemicarbazones: syntheses, characterization and cytotoxicity against breast cancer cells and Anti-Mycobacterium tuberculosis activity

Three PdII complexes were prepared from N(4)-substituted thiosemicarbazones: [Pd(aptsc)(PPh3)](NO3) H2O, 1, [Pd(apmtsc)(PPh3)](NO3), 2, and [Pd(apptsc)(PPh3)](NO3) H2O, 3, where PPh3 = triphenylphosphine; Haptsc = 2-acetylpyridine-thiosemicarbazone; Hapmtsc = 2-acetylpyridine-N(4)-methyl-thiosemicar...

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Access type:openAccess
Publication Date:2010
Main Author: Maia, Pedro I. da S.
Other Authors: Graminha, Angélica, Pavan, Fernando R., Leite, Clarice Q. F., Batista, Alzir A., Back, Davi F., Lang, Ernesto S., Ellena, Javier, Lemos, Sebastião de S., Salistre-de-Araujo, Heloisa S., Deflon, Victor M.
Document type: Article
Language:eng
Published: Sociedade Brasileira de Química
Online Access:http://repositorio.unb.br/handle/10482/27751
https://dx.doi.org/10.1590/S0103-50532010000700004
Citation:J. Braz. Chem. Soc.,v.21,n.7,p.1177-1186,2010
Portuguese abstract:Three PdII complexes were prepared from N(4)-substituted thiosemicarbazones: [Pd(aptsc)(PPh3)](NO3) H2O, 1, [Pd(apmtsc)(PPh3)](NO3), 2, and [Pd(apptsc)(PPh3)](NO3) H2O, 3, where PPh3 = triphenylphosphine; Haptsc = 2-acetylpyridine-thiosemicarbazone; Hapmtsc = 2-acetylpyridine-N(4)-methyl-thiosemicarbazone and Happtsc = 2-acetylpyridine-N(4)-phenyl-thiosemicarbazone. All complexes were characterized by elemental analysis, IR, UV-Vis, ¹H and 31P{¹H} NMR spectroscopies, and had their crystalline structures determined by X-ray diffractometry from single crystals. The monoanionic thiosemicarbazonate ligands act in a tridentate mode, binding to the metal through the pyridine nitrogen, the azomethine nitrogen and the sulfur atoms. The cytotoxic activity against the breast cancer cell line MDA-MB231 and the anti-Mycobacterium tuberculosis H37Rv ATCC 27294 activity were evaluated for the compounds. All PdII complexes were highly active against the studied cell line, presenting similar values of IC50, around 5 µmol L-1, while the clinically applied antitumor agent cisplatin was inactive. The compounds show remarkable anti-M. tuberculosis activities, presenting MIC values comparable or better than some commercial anti-M tuberculosis drugs.
Três complexos de PdII com tiossemicarbazonas N(4)-substituídas foram preparados: [Pd(aptsc)(PPh3)](NO3) H2O, 1, [Pd(apmtsc)(PPh3)](NO3), 2, e [Pd(apptsc)(PPh3)](NO3) H2O, 3, sendo PPh3 = trifenilfosfina; Haptsc = 2-acetilpyridina-tiossemicarbazona; Hapmtsc = 2-acetilpiridina-N(4)-metil-tiossemicarbazona e Happtsc = 2-acetilpiridina-N(4)-fenil-tiossemicarbazona. Os complexos foram caracterizados por análise elementar, IR, UV-Vis, ¹H e 31P{¹H} NMR e tiveram suas estruturas cristalinas determinadas por difratometria de raios X em monocristal. Os ligantes tiossemicarbazonatos monoaniônicos atuam de modo tridentado, ligando-se ao metal pelos átomos de nitrogênio piridínico, nitrogênio azometínico e enxofre. A atividade citotóxica frente à linhagem de células tumorais MDA-MB231 (tumor de mama) e a atividade anti-Mycobacterium tuberculosis H37Rv ATCC 27294 dos compostos foram investigadas. Os complexos de PdII mostraram-se altamente ativos contra as células tumorais, com valores de IC50 em torno de 5 µmol L-1, enquanto o agente antitumoral em uso clínico cisplatina mostrou-se inativo. Os compostos apresentaram atividade anti-M. tuberculosis significante, com valores de CIM comparáveis ou melhores que aqueles referentes a alguns fármacos usados clinicamente contra tuberculose.