Cytotoxic activity of Ru(II)/DPEPhos/N,S-mercapto complexes (DPEPhos = bis-[(2-diphenylphosphino)phenyl]ether).

Autor: Grawe GF; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13561-901, São Carlos, SP, Brazil., Oliveira KM; Instituto de Química, Universidade de Brasília (UnB) - Campus Darcy Ribeiro, CEP 70910-900, Brasília, DF, Brazil; Instituto de Física de São Carlos, Universidade de São Paulo - USP, CEP 13560-970, São Carlos, SP, Brazil. Electronic address: katia.oliveira@unb.br., Leite CM; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13561-901, São Carlos, SP, Brazil., de Oliveira TD; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13561-901, São Carlos, SP, Brazil., Costa AR; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13561-901, São Carlos, SP, Brazil., Moraes CAF; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13561-901, São Carlos, SP, Brazil., Honorato J; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13561-901, São Carlos, SP, Brazil; Instituto de Física de São Carlos, Universidade de São Paulo - USP, CEP 13560-970, São Carlos, SP, Brazil., Cominetti MR; Departamento de Gerontologia, Universidade Federal de São Carlos (UFSCar), CEP 13565-905, São Carlos, SP, Brazil., Castellano EE; Instituto de Física de São Carlos, Universidade de São Paulo - USP, CEP 13560-970, São Carlos, SP, Brazil., Correa RS; Departamento de Química, ICEB, Universidade Federal de Ouro Preto (UFOP), CEP 35400-000, Ouro Preto, MG, Brazil., Machado SP; Instituto de Química, Universidade Federal do Rio de Janeiro - UFRJ, CEP 21941-909, Rio de Janeiro, RJ, Brazil., Batista AA; Departamento de Química, Universidade Federal de São Carlos - UFSCar, CEP 13561-901, São Carlos, SP, Brazil. Electronic address: daab@ufscar.br.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2023 Jul; Vol. 244, pp. 112204. Date of Electronic Publication: 2023 Mar 30.
DOI: 10.1016/j.jinorgbio.2023.112204
Abstrakt: We report here on three new ruthenium(II) complexes, [Ru(DPEPhos)(mtz)(bipy)]PF 6 (Ru1), [Ru(DPEPhos)(mmi)(bipy)]PF 6 (Ru2) and [Ru(DPEPhos)(dmp)(bipy)]PF 6 (Ru3). DPEPhos = bis-[(2-diphenylphosphino)phenyl]ether, mtz = 2-mercapto-2-thiazoline, mmi = 2-mercapto-1-methylimidazole, dmp = 4,6-diamino-2-mercaptopyrimidine and bipy = 2,2'-bipyridine. The compounds were characterized by several spectroscopic techniques, and the molecular structure of Ru1 complex was determined by single-crystal X-ray diffraction. The cytotoxicity of Ru1 - Ru3 complexes were tested against the A549 (human lung) and the MDA-MB-231 (human breast) cancer cell lines and against MRC-5 (non-tumor lung) and MCF-10A (non-tumor breast) cell lines through the MTT assay. All three complexes are cytotoxic against the cell lines studied, with IC 50 values lower than those found for the cisplatin. Among them, the Ru2 complex has shown the best selectivity against MDA-MB-231 cancer cell lines, with an IC 50 value 12 times lower than that on MCF-10A. The complex Ru2 was capable to induce changes in MDA-MB-231 cells morphology, with loss of cellular adhesion, inhibited colony formation and induce an accumulation of cells at the sub-G1 phase, with an increase in S-phase and decrease of cells at G2 phase. Viscosity, electrochemical and Hoechst 33258 displacement experiments for Ru1 - Ru3 complexes with calf thymus DNA (CT-DNA) showed an electrostatic and groove binding mode of interaction. Additionally, the complexes interact with the protein Human Serum Albumin (HSA) by static mechanism. The negative values for ΔH and ΔS indicate that van der Waals forces and hydrogen bonding may occurs between the complexes and HSA. Therefore, this class of complexes are promising anticancer candidates and may be selected to further detailed studies.
Competing Interests: Declaration of Competing Interest There are no conflicts to declare.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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