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

Abstract

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 1.0-4.9×10(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.

• Authors: Rodrigo S Corrêa, Monize M da Silva, Angelica E Graminha, Cássio S Meira, Jamyle A F Dos Santos, Diogo R M Moreira, Milena B P Soares, Gustavo Von Poelhsitz, Eduardo E Castellano, Carlos Bloch Jr, Marcia R Cominetti, Alzir A Batista
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 156 Pg. 153-63 (Mar 2016) ISSN: 1873-3344 [Electronic] United States
• PMID: 26795676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Antiprotozoal Agents
• Ruthenium Compounds
• Thiazolidines
• 2-mercaptothiazoline

Topics

• Antineoplastic Agents (pharmacology)
• Antiprotozoal Agents (pharmacology)
• Crystallography, X-Ray
• Drug Screening Assays, Antitumor
• Humans
• MCF-7 Cells
• Ruthenium Compounds (chemistry)
• Thiazolidines (chemistry)
• Trypanosoma cruzi (drug effects)