Autor(es): Correa, Rodrigo de Souza ; Silva, Monize Martins da ; Graminha, Angelica Ellen ; Meira, Cássio Santana ; Santos, Jamyle Andrade Ferreira dos ; Moreira, Diogo Rodrigo de Magalhães ; Soares, Milena Botelho Pereira ; Poelhsitz, Gustavo Von ; Castellano, Eduardo Ernesto ; Bloch Junior, Carlos ; Cominetti, Márcia Regina ; Batista, Alzir Azevedo
Data: 2016
Origem: Oasisbr
Assunto(s): Cytotoxicity; Trypanosoma cruzi
Three newmixed 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 (Kb) values in range of 1.0–4.9 × 103 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.
