Issue 18, 2019

In vitro cytotoxicity and in vivo zebrafish toxicity evaluation of Ru(ii)/2-mercaptopyrimidine complexes

Abstract

In this paper, four new ruthenium complexes, [Ru(N–S)(dppm)2]PF6 (1), [Ru(N–S)(dppe)2]PF6 (2), [Ru(N–S)2(dppp)] (3) and [Ru(N–S)2(PPh3)2] (4) [dppm = 1,1-bis(diphenylphosphino)methane, dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, PPh3 = triphenylphosphine and N–S = 2-mercaptopyrimidine anion] were synthesized and characterized using spectroscopy techniques, molar conductance, elemental analysis, electrochemical techniques and X-ray diffraction. The DNA binding studies were investigated using voltammetry and spectroscopy techniques. The results show that all complexes exhibit a weak interaction with DNA. HSA interaction with the complexes was studied using fluorescence emission spectroscopy, where the results indicate a spontaneous interaction between the species by a static quenching mechanism. The cytotoxicity of the complexes was evaluated against A549, MDA-MB-231 and HaCat cells by MTT assay. Complexes (1) and (2), which are very active against triple negative MDA-MB-231, were subjected to further biological tests with this cell line. The cytotoxic activity triggered by the complexes was confirmed by clonogenic assay. Cell cycle analyses demonstrated marked anti-proliferative effects, especially at the G0/G1 and S phases. The morphological detection of apoptosis and necrosis – HO/PI and Annexin V-FITC/PI assay, elucidated that the type of cell death triggered by these complexes was probably by apoptosis. The in vivo toxicological assessment performed on zebrafish embryos revealed that complexes (1) and (2) did not present embryotoxic or toxic effects during embryonic and larval development showing that they are promising new prototypes of safer and more effective drugs for triple negative breast cancer treatment.

Graphical abstract: In vitro cytotoxicity and in vivo zebrafish toxicity evaluation of Ru(ii)/2-mercaptopyrimidine complexes

Supplementary files

Article information

Article type
Paper
Submitted
15 set 2018
Accepted
21 jan 2019
First published
31 jan 2019

Dalton Trans., 2019,48, 6026-6039

In vitro cytotoxicity and in vivo zebrafish toxicity evaluation of Ru(II)/2-mercaptopyrimidine complexes

V. S. Velozo-Sá, L. R. Pereira, A. P. Lima, F. Mello-Andrade, M. R. M. Rezende, R. M. Goveia, W. C. Pires, M. M. Silva, K. M. Oliveira, A. G. Ferreira, J. Ellena, V. M. Deflon, C. K. Grisolia, A. A. Batista and E. P. Silveira-Lacerda, Dalton Trans., 2019, 48, 6026 DOI: 10.1039/C8DT03738H

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