New ruthenium complexes containing salicylic acid and derivatives induce triple-negative tumor cell death via the intrinsic apoptotic pathway.

Autor: Graminha AE; Gerontology Department, Federal University of São Carlos, CP, 13565-905, São Carlos, SP, Brazil; Chemistry Department, Federal University of São Carlos, CP, 13565-905, São Carlos, SP, Brazil. Electronic address: aegraminha@gmail.com., Popolin C; Gerontology Department, Federal University of São Carlos, CP, 13565-905, São Carlos, SP, Brazil. Electronic address: ceciliapopolin@gmail.com., Honorato de Araujo-Neto J; São Carlos Institute of Physics, University of São Paulo, CP, 13566-590, São Carlos, SP, Brazil., Correa RS; Chemistry Department, Federal University of Ouro Preto, CP, 35.400-000, Ouro Preto, MG, Brazil., de Oliveira KM; Chemistry Department, Federal University of São Carlos, CP, 13565-905, São Carlos, SP, Brazil; Chemistry Department, Federal University of Ouro Preto, CP, 35.400-000, Ouro Preto, MG, Brazil., Godoy LR; Gerontology Department, Federal University of São Carlos, CP, 13565-905, São Carlos, SP, Brazil., Vegas LC; Institute of Chemistry, Federal University of Rio Grande do Sul, CP, 91501-970, Porto Alegre-RS, Brazil., Ellena J; São Carlos Institute of Physics, University of São Paulo, CP, 13566-590, São Carlos, SP, Brazil., Batista AA; Chemistry Department, Federal University of São Carlos, CP, 13565-905, São Carlos, SP, Brazil., Cominetti MR; Gerontology Department, Federal University of São Carlos, CP, 13565-905, São Carlos, SP, Brazil.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2022 Dec 05; Vol. 243, pp. 114772. Date of Electronic Publication: 2022 Sep 16.
DOI: 10.1016/j.ejmech.2022.114772
Abstrakt: In this work we present the synthesis and characterization of six new ruthenium compounds with general formulae [Ru(L)(dppb)(bipy)]PF 6 and [Ru(L)(dppe) 2 ]PF 6 where L = salicylic acid (Sal), 4-aminosalicylic acid (AmSal) or 2,4-dihydroxybenzoic acid (DiSal), dppb = 1,4-bis(diphenylphosphino)butane, dppe = 1,2-bis(diphenylphosphino)ethane and bipy = 2,2'-bipyridine. The complexes were characterized by elemental analysis, molar conductivity, cyclic voltammetry, NMR, UV-vis and IR spectroscopies, and two by X-ray crystallography. The 31 P{ 1 H} NMR spectra of the complexes with the general formula [Ru(L)(dppe) 2 ]PF 6 showed that the phosphorus signals are solvent-dependent. Aprotic solvents, which form strong hydrogen bonds with the complexes, inhibit the free rotation of the salicylic acid-based, modifying the diphosphine cone angles, leading to distortion of the phosphorus signals in the NMR spectra. The cytotoxicity of the complexes was evaluated in MCF-7, MDA-MB-231, SKBR3 human breast tumor cells, and MCF-10 non-tumor cell lines. The complexes with the structural formula [Ru(L)(dppe) 2 ]PF 6 were the most cytotoxic, and the complex [Ru(AmSal)(dppe) 2 ]PF 6 with L = 4-aminosalicylic acid ligand was the most selective for the MDA-MB-231 cell line. This complex interacts with the transferrin and induces apoptosis through the intrinsic pathway, as demonstrated by increased levels of proteins involved in apoptotic cell death.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Databáze: MEDLINE
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