Cytotoxic Ruthenium(II)-Diphosphine Complexes Affect the Mitochondrial Respiration of Lung Cancer Cells

Autor(es)

Palmeira-Mello, Marcos V. ; Mesdom, Pierre ; Burckel, Pierre ; Hidalgo, Samia ; Blacque, Olivier ; Gasser, Gilles ; Batista, Alzir A.

• Tipo de documento: Artigo Científico
• Fonte: CHEMBIOCHEM; v. 26, n. 2, p. 14-pg., 2025-01-10.

Resumo

In this work, we studied six Ruthenium(II)-diphosphine compounds containing different mercapto ligands (N-S), with general formula [Ru(N-S)(dppm)2]Cl (dppm=1,1-bis(diphenylphosphino)methane). These compounds were characterized by several techniques (NMR [1H, 31P(1H), and 13C], HRMS, IR, UV-Vis and XRD) and their purity confirmed by elemental analysis. DLS experiments revealed low diameters and polydispersity indexes, and positive log P values in n-octanol/PBS indicated their preference for the organic phase. In general, these compounds are stable in different media over 48 h. Cytotoxicity experiments revealed promising IC50 values on A549 breast cancer cells, 0.48 mu M and 0.80 mu M for [Ru(mtz)(dppm)2]Cl (1) and [Ru(mmi)(dppm)2]Cl (2), respectively (mtz and mmi are 2-mercapto-2-thiazoline and mercapto-1-methylimidazole in their deprotonated form, respectively). Clonogenic and migration experiments indicated their antiproliferative and anti-migratory capacity. ICP-MS results indicated their cellular accumulation in the nucleus, with little amounts in mitochondria. No covalent DNA binding was observed by ICP-MS. JC-1 and cell Mito Stress test confirmed mitochondrial dysfunction, which was verified by mitochondrial membrane potential uncoupling and drastic alterations in the oxygen consumption rate. Taken together, our results provide crucial insights regarding the anticancer potential of ruthenium(II)-phosphine compounds. (AU)

• Processo FAPESP: 22/02876-0 - Avaliação do perfil biológico de complexos de coordenação: uma abordagem em modelos celulares 2D e 3D
• Beneficiário: Fillipe Vieira Rocha
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/01787-0 - Estudo in vitro e in vivo de complexos fosfínicos de Ru(II) com atividades anticancerígenas
• Beneficiário: Marcos Vinícius Palmeira de Mello
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 22/09971-8 - Investigação de complexos baseados em rutênio(II) como candidatos a quimioterapia anticâncer: do design aos estudos biológicos/bioquímicos
• Beneficiário: Marcos Vinícius Palmeira de Mello
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 23/02475-8 - Complexos fosfínicos de Ru(II) com naftoquinonas e derivados: potenciais anticancerígenos, estudos in vitro e in vivo
• Beneficiário: Alzir Azevedo Batista
• Modalidade de apoio: Auxílio à Pesquisa - Regular