| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1316435 | Journal of Inorganic Biochemistry | 2016 | 11 Pages |
•Mononuclear and mixed Ru(II) complexes with 1,3-thiazolidine-2-thione•Promising agents against prostate (DU-145) and breast (MCF-7) tumor cells•Antiparasitic activity against T. cruzi exhibiting a broad spectrum of action•Parasite death induced by necrotic process.•Combining Ru(II) complexes with benznidazole enhances anti-T. cruzi activity.
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 (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.
Graphical abstractThree new 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. These complexes demonstrated elevated cytotoxicity against cancer cell lines and also antiparasitic activity against Trypanosoma cruzi that can be improved by benznidazole combination. Additionally, complex 3 caused parasite cell death through a necrotic process.Figure optionsDownload full-size imageDownload as PowerPoint slide
