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

Autor(es)

Graminha, Angelica E. ; Popolin, Cecilia ; de Araujo-Neto, Joao Honorato ; Correa, Rodrigo S. ; de Oliveira, Katia M. ; Godoy, Luani R. ; Vegas, Legna Colina ; Ellena, Javier ; Batista, Alzir A. ; Cominetti, Marcia R.

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 243, p. 14-pg., 2022-12-05.

Resumo

In this work we present the synthesis and characterization of six new ruthenium compounds with general formulae [Ru(L)(dppb)(bipy)]PF6 and [Ru(L)(dppe)2]PF6 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 31P{1H} NMR spectra of the complexes with the general formula [Ru(L)(dppe)2]PF6 showed that the phosphorus signals are solvent-dependent. Aprotic solvents, which form strong hydrogen bonds with the com-plexes, 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]PF6 were the most cytotoxic, and the complex [Ru(AmSal)(dppe)2]PF6 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. (AU)

• Processo FAPESP: 17/15850-0 - Difração de raios X como ferramenta no desenvolvimento de potenciais fármacos
• Beneficiário: Eduardo Ernesto Castellano
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/19632-0 - Novos complexos de rutênio com ligantes bioativos: investigação do mecanismo de ação
• Beneficiário: Angelica Ellen Graminha
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 21/04876-4 - Estudos sobre estrutura & atividade de complexos de RuII/areno/mercaptoligantes frente ao câncer
• Beneficiário: João Honorato de Araujo Neto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 20/14561-8 - Estudo in vitro e in vivo de complexos fosfínicos de Ru(II) com atividades anticancerígenas
• Beneficiário: Alzir Azevedo Batista
• Modalidade de apoio: Auxílio à Pesquisa - Regular