In vitro SOD-like activity of mono- and di-copper complexes with a phosphonate substituted SALAN-type ligand

• Published in: Chemico-biological interactions 2019-06, Vol.306, p.78-88
• Main Authors: Székács, Inna, Tokarz, Paweł, Horvath, Robert, Kovács, Krisztina, Kubas, Adam, Shimura, Mari, Brasun, Justyna, Murzin, Vadim, Caliebe, Wolfgang, Szewczuk, Zbigniew, Paluch, Aneta, Wojnárovits, László, Tóth, Tünde, Pap, József S., Szyrwiel, Łukasz
• Format: Article
• Language: English
• Subjects: Antioxidant; Cu-complex; In vitro cytotoxicity; SALAN; SOD-Like activity
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2019.04.003

SALEN- and SALAN-based complexes with catalytically active metal centers are very promising small molecules to be utilized as part of antioxidant therapies. Here we discuss a modified SALAN-type molecule armed with two phosphonate groups that significantly increase its water solubility and aid to furnish mono- or dinuclear complexes with Cu2+ ions. The regulation of the SOD-mimicking (i.e., catalytic) disproportionation reaction of the superoxide radical anion (O2•−) at pH ~7.5 could be achieved by adjusting the metal-to-ligand stoichiometry as confirmed by McCord-Fridovich and pulse radiolysis tests. The higher antioxidant activity of the dicopper complex can be explained by the better access of O2•− to the copper centers and their more positive Cu(II)/Cu(I) redox potential. Simultaneously the analysis of in vitro effect on cells morphology indicates that cytotoxicity is also affected by the metal-to-ligand ratio, however, the active complex molecules do not show notable cytotoxicity that, together with the observed SOD-like activities, makes them potential candidates for antioxidant therapies. [Display omitted] •Phosphonate groups affect coordination of Cu(II) to a SALAN ligand and increase water solubility.•SOD-like activity and overall cell toxicity are both affected by Cu/ligand ratio.•The SOD-mimc 1Cu/ligand complex is well tolerated by living cells.