Copper(I)/Triphenylphosphine Complexes Containing Naphthoquinone Ligands as Potential Anticancer Agents

Autor(es)

Leite, Celisnolia M. ; Araujo-Neto, Joao H. ; Guedes, Adriana P. M. ; Costa, Analu R. ; Demidoff, Felipe C. ; Netto, Chaquip D. ; Castellano, Eduardo E. ; Nascimento, Otaciro R. ; Batista, Alzir A.

• Tipo de documento: Artigo Científico
• Fonte: INORGANICS; v. 11, n. 9, p. 18-pg., 2023-09-01.

Resumo

Four new Cu/PPh3/naphtoquinone complexes were synthesized, characterized (IR, UV/visible, 1D/2D NMR, mass spectrometry, elemental analysis, and X-ray diffraction), and evaluated as anticancer agents. We also investigated the reactive oxygen species (ROS) generation capacity of complex 4, considering the well-established photochemical property of naphthoquinones. Therefore, employing the electron paramagnetic resonance (EPR) "spin trap", 5,5-dimethyl-1-pyrroline N-oxide (DMPO) technique, we identified the formation of the characteristic & BULL;OOH species (hydroperoxyl radical) adduct even before irradiating the solution containing complex 4. As the irradiation progressed, this radical species gradually diminished, primarily giving rise to a novel species known as & BULL;DMPO-OH (DMPO + & BULL;OH radical). These findings strongly suggest that Cu(I)/PPh3/naphthoquinone complexes can generate ROS, even in the absence of irradiation, potentially intensifying their cytotoxic effect on tumor cells. Interpretation of the in vitro cytotoxicity data of the Cu(I) complexes considered their stability in cell culture medium. All of the complexes were cytotoxic to the lung (A549) and breast tumor cell lines (MDA-MB-231 and MCF-7). However, the higher toxicity for the lung (MRC5) and breast (MCF-10A) non-tumoral cells resulted in a low selectivity index. The morphological analysis of MDA-MB-231 cells treated with the complexes showed that they could cause decreased cell density, loss of cell morphology, and loss of cell adhesion, mainly with concentrations higher than the inhibitory concentration of 50% of cell viability (IC50) values. Similarly, the clonogenic survivance of these cells was affected only with concentrations higher than the IC50 values. An antimigratory effect was observed for complexes 1 and 4, showing around 20-40% of inhibition of wound closure in the wound healing experiments. (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: 22/11924-8 - Complexos mercapto/nitrosilo de rutênio: avaliação in vitro e in vivo da atividade antitumoral
• Beneficiário: Alex Marchezini Graça
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• 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