Ruthenium(II) complexes of 1,3-thiazolidine-2-thione: Cytotoxicity against tumor cells and anti-Trypanosoma cruzi activity enhanced upon combination with benznidazole

Autor(es):Mostrar menos -

Correa, Rodrigo S. ^{[1, 2]} ; da Silva, Monize M. ^[2] ; Graminha, Angelica E. ^[2] ; Meira, Cassio S. ^[3] ; dos Santos, Jamyle A. F. ^[3] ; Moreira, Diogo R. M. ^[3] ; Soares, Milena B. P. ^{[3, 4]} ; Von Poelhsitz, Gustavo ^[5] ; Castellano, Eduardo E. ^[6] ; Bloch, Jr., Carlos ^[7] ; Cominetti, Marcia R. ^[8] ; Batista, Alzir A. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Ouro Preto, ICEB, Dept Quim, BR-35400000 Ouro Preto, MG - Brazil

^[2] Univ Fed Sao Carlos, Dept Quim, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[3] Fiocruz MS, Ctr Pesquisas Goncalo Moniz, BR-40296710 Salvador, BA - Brazil

^[4] Hosp Sao Rafael, Ctr Biotecnol & Terapia Celular, Ave Sao Rafael 2152, BR-41253190 Salvador, BA - Brazil

^[5] Univ Fed Uberlandia, Inst Quim, CP 593, BR-38400902 Uberlandia, MG - Brazil

^[6] Univ Sao Paulo, Inst Fis, CP 369, BR-13560970 Sao Carlos, SP - Brazil

^[7] EMBRAPA, Ctr Nacl Pesquisa Recursos Genet & Biotecnol, Estacao Parque Biol, BR-70910900 Brasilia, DF - Brazil

^[8] Univ Fed Sao Carlos, Dept Gerontol, CP 676, BR-13565905 Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Inorganic Biochemistry; v. 156, p. 153-163, MAR 2016.
• Citações Web of Science: 26

Resumo

Three new mixed and mononuclear Ru(II) complexes containing 1,3-thiazolidine-2-thione (tzdtH) were synthesized and characterized by spectroscopic analysis, molar conductivity, cyclic voltammetry, high-resolution electrospray ionization mass spectra and X-ray diffraction. The complexes presented unique stereochemistry and the proposed formulae are: {[}Ru(tzdt)(bipy)(dppb)]PF6 (1), cis-{[}Ru(tzdt)(2)(PPh3)(2)] (2) and trans{[}Ru(tzdt)(PPh3)(2)(bipy)]PF6 (3), where dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2'-bipyridine. These complexes demonstrated strong cytotoxicity against cancer cell lines when compared to cisplatin. Specifically, complex 2 was the most potent cytotoxic agent against MCF-7 breast cells, while complexes 1 and 3 were more active in DU-145 prostate cells. Binding of complexes to ctDNA was determined by UV-vis titration and viscosity measurements and revealed binding constant (K-b) values in range of 1.0-4.9 x 10(3) M-1, which are characteristic of compounds possessing weak affinity to ctDNA. In addition, these complexes presented antiparasitic activity against Trypanosoma cruzi. Specifically, complex 3 demonstrated strong potency, moderate selectivity index and acted in synergism with the approved antiparasitic drug, benznidazole. Additionally, complex 3 caused parasite cell death through a necrotic process. In conclusion, we demonstrated that Ru(II) complexes have powerful pharmacological activity, while the metal-free tzdtH does not provoke the same outcome. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 12/06013-4 - Estudo da expressão de genes de apoptose, ciclo celular, reparo do DNA e estresse oxidativo em células de carcinoma de pulmão humano tratadas com complexos de fórmula geral [Ru(AA)(dppb)(bipy)]PF6
• Beneficiário: Alzir Azevedo Batista
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/08131-1 - Complexos de rutênio com ligantes de interesse biológico: aspectos químicos, estruturais e avaliação de suas citotoxicidades em células tumorais
• Beneficiário: Rodrigo de Souza Corrêa
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/26559-4 - Modificações estruturais em complexos de Ru(II) biologicamente ativos para o desenho de novos candidatos a metalofármacos
• Beneficiário: Rodrigo de Souza Corrêa
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado