"Half-Sandwich"/Ru-II Anticancer Complexes Containing Triphenylphosphine and p-Substituted Benzoic Acids

Autor(es)

Honorato, Joao ; Oliveira, Katia M. ; Leite, Celisnolia M. ; Colina-Vegas, Legna ; Nobrega, Joaquim A. ; Castellano, Eduardo E. ; Ellena, Javier ; Correa, Rodrigo S. ; Batista, Alzir A.

• Tipo de documento: Artigo Científico
• Fonte: Journal of the Brazilian Chemical Society; v. 31, n. 11, p. 13-pg., 2020-11-01.

Resumo

Mononuclear and binuclear Ru-II/arene/triphenylphosphine complexes with p-substituted benzoic acid derivatives were prepared and characterized. These monocationic complexes of type [Ru(eta(6)-p-cymene)(PPh3)L] (L = benzoic acid (1), p-hydroxybenzoic acid (2), p-nitrobenzoic acid (3) and terephthalic acid (4)) were characterized using various techniques, such as nuclear magnetic resonance (NMR) and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, and the crystal structure of 1, 3 and 4 were determined by X-ray diffraction analysis. The cytotoxicity of the complexes was evaluated, in vitro, against tumorigenic [MDA-MB-231, MCF-7 (breast), A549 (lung) and DU-145 (prostate)] and non-tumorigenic [MCF-10A (breast), MRC-5 (lung) and PNT-2 (prostate)] cells. The binuclear complex (4) was inactive due to its low solubility. Complexes 1, 2 and 3 showed similar cytotoxicity, however, complex 1 presented better selectivity index against MDA-MB-231 than compounds 2 and 3. Cellular ruthenium absorption was explored by inductively coupled plasma mass spectrometry (ICP-MS) analyzing the whole cells and the culture medium. Complementary studies showed that complex 1 inhibited colony formation, induced morphology changes in cells and promoted cell cycle arrest in the Sub-G1 phase for the MDA-MB-231 cells. (AU)

• Processo FAPESP: 16/23130-5 - Determinação da biodistribuição celular de Cu, Ru e Pt em células humanas tumorais e não tumorais de mama mediante a técnica de espectrometria de massas com plasma acoplado indutivamente
• Beneficiário: Legna Andreina Colina Vegas
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado