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

Author(s):Show less -

Velozo-Sa, Vivianne S. ^[1] ; Pereira, Luciano R. ^[2] ; Lima, Aliny P. ^[3] ; Mello-Andrade, Francyelli ^[1] ; Rezende, Manuela R. M. ^[1] ; Goveia, Rebeca M. ^[1] ; Pires, Wanessa C. ^[1] ; Silva, Monize M. ^[2] ; Oliveira, Katia M. ^[2] ; Ferreira, Antonio G. ^[2] ; Ellena, Javier ^[4] ; Deflon, Victor M. ^[5] ; Grisolia, Cesar Koppe ^[6] ; Batista, Alzir A. ^[2] ; Silveira-Lacerda, Elisangela P. ^[1]

Affiliation

^[1] Fed Univ Goias UFG, Lab Mol Genet & Cytogenet, Inst Biol Sci, BR-74690900 Goiania, Go - Brazil

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

^[3] Fac Brazil Inst, BR-75133050 Anapolis, Go - Brazil

^[4] Univ Sao Paulo, Phys Inst Sao Carlos, CP 369, BR-13560970 Sao Carlos, SP - Brazil

^[5] Univ Sao Paulo, Chem Inst, CP 780, BR-13560970 Sao Carlos, SP - Brazil

^[6] Univ Brasilia, Lab Toxicol Genet, Dept Genet & Morphol, Inst Biol Sci, BR-70910900 Brasilia, DF - Brazil

• Document type: Journal article
• Source: DALTON TRANSACTIONS; v. 48, n. 18, p. 6026-6039, MAY 14 2019.
• Web of Science Citations: 7

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. (AU)

• FAPESP's process: 14/04147-9 - Evaluation of anticancer properties of ruthenium(II)complexes containing lapachol and lawsone bioligands
• Grantee: Katia Mara de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/16312-0 - CYTOTOXICITY AND MECHANISM OF ACTION OF RUTHENIUM COMPLEXES CONTAINING NATURAL PRODUCTS OR DERIVATIVES
• Grantee: Alzir Azevedo Batista
• Support Opportunities: Regular Research Grants