Comparative Study of Antioxidant and Pro-Oxidant Properties of Homoleptic and Heteroleptic Copper Complexes with Amino Acids, Dipeptides and 1,10-Phenanthroline: The Quest for Antitumor Compounds

Autor(es)

Veiga, Nicolas ^[1] ; Alvarez, Natalia ^[1] ; Castellano, Eduardo E. ^[2] ; Ellena, Javier ^[2] ; Facchin, Gianella ^[1] ; Torre, Maria H. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Republica, Fac Quim, DEC, Quim Inorgan, Av Gral Flores 2124, Montevideo 11800 - Uruguay

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, Lab Multiusuario Cristalog Estrutura, BR-13566590 Sao Carlos - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 26, n. 21 NOV 2021.
• Citações Web of Science: 0

Resumo

In a search for new antitumoral agents, a series of homoleptic copper(II) complexes with amino acids and dipeptides, as well as heteroleptic complexes containing both dipeptides and 1,10-phenanthroline, were studied. Furthermore, a single-crystal structure containing alanyl-leucinato ({[}Cu-3(AlaLeu)(3)(H2O)(3)(CO3)]\& BULL;PF6 \& BULL;H2O), which is the first homotrinuclear carbonato-bridged copper(II) complex with a dipeptide moiety, is presented. To assess possible antitumor action mechanisms, we focused on the comparative analysis of pro- and antioxidant behaviors. Pro-oxidant activity, in which the reactive oxygen species (ROS) formed by the reaction of the complexes with H2O2 produce oxidative damage to 2-deoxy-d-ribose, was evaluated using the TBARS method. Additionally, the antioxidant action was quantified through the superoxide dismutase (SOD)-like activity, using a protocol based on the inhibitory effect of SOD on the reduction of nitrobluetetrazolium (NBT) by the superoxide anion generated by the xanthine/xanthine oxidase system. Our findings show that Cu-amino acid complexes are strong ROS producers and moderate SOD mimics. Conversely, Cu-dipeptide-phen complexes are good SOD mimics but poor ROS producers. The activity of Cu-dipeptide complexes was strongly dependent on the dipeptide. A DFT computational analysis revealed that complexes with high SOD-like activity tend to display a large dipole moment and condensed-to-copper charge, softness and LUMO contribution. Moreover, good ROS producers have higher global hardness and copper electrophilicity, lower copper softness and flexible and freely accessible coordination polyhedra.</p> (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