Compostos de paládio(II) contendo acetofenonaoxima ortometalada: síntese, caracterização e avaliação da atividade citotóxica

• Autor(a) principal: Souza, Ronan Farias Freire de [UNESP]
• Data de Publicação: 2017
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://hdl.handle.net/11449/151865
• topic: Ciclopaladados; Oximas; Atividade antitumoral; Acetofenonaoxima; Ligantes sulfurados; Cyclopalladated; Oximes; Antitumor activity; Acetophenoneoxime; Sulfur ligands

Cyclometallated Pd(II) compounds are of great interest, specially, for their extensive applications in various science areas. Cyclopalladated compounds consist of a class of palladium(II) chelates with potencial medicinal uses since many of them exhibit antitumor activity comparable or superior to cisplatin (main atineoplastic agent) and significant antimycobacterial and antiprotozoal activities as well. In this context, the present work aimed at to synthesize fourteen novel cyclopalladated species of the type [Pd(X)(C2,N-afox)(X)(L)], where C2,N-afox = acetophenoneoxime, L = thiourea (tu); N-methylthiourea (mtu); N,N’-dimethylthiourea (dmtu); N-phenylthiourea (ftu); N,N’-diphenylthiourea (dftu); thioacetamide (taa) and thiobenzamide (tbz) and X = Cl- or I-. Their structures were proposed by C, H and N elemental analysis, thermal analysis (thermogravimetric and differential), infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy. Single-crystal X-ray diffraction studies were carried out for [PdCl(C2,N-afox)(L)], where L = (tu), (dmtu) and (taa). The in vitro cytotoxic activity was evaluated against MRC-5 (human lung fibroblast), HepG2 (liver hepatocellular carcinoma), Cal27 (oral adenosquamous carcinoma), 4T1 (mammary carcinoma), B16F10-Nex2 (murine melanoma), A2058 (human melanoma) and Sk-Mel-110 / Sk-Mel-05 (human metastatic melanomas). The results showed that compounds with methyl and phenyl groups in the thiocarbonylated ligand tend to be more cytotoxic than cisplatin (standard drug) and the exchange of chloride by iodide in the palladium coordination sphere favored the compounds activity. Cell cycle assays were performed, revealing that the complexes act on the sub-G1 cycle phase and that the cells die in sub-G1/G1 without necessarily duplicate the DNA and hemolysis assays in healthy blood cells, indicating that chloro-complexes in general didn’t show significant hemolytic action. In addition, the incorporation of the chloro-complexes bearing (tu), (dmtu) and (dftu) into nanostructured lipid systems revealed that their selectivity against HepG2 increased three-fold compared to cisplatin, showing that the association of these lipid systems with palladium(II) compounds may be of interest in the cancer treatment.