Macrocyclic copper(II) complexes

Superoxide scavenging activity, structural studies and cytotoxicity evaluation

Ana S. Fernandes, Jorge Gaspar, M. Fátima Cabral, Cátia Caneiras, Rita Guedes, José Rueff, Matilde Castro, Judite Costa, Nuno G. Oliveira

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Synthetic superoxide dismutase mimetics have emerged as a potential novel class of drugs for the treatment of oxidative stress related diseases. Among these agents, metal complexes with macrocyclic ligands constitute an important group. In this work we synthesized five macrocyclic copper(II) complexes and evaluated their ability to scavenge the superoxide anions generated by the xanthine-xanthine oxidase system. Two different endpoints were used, the nitro blue tetrazolium (NBT) reduction assay (colorimetric method) and the dihydroethidium (DHE) oxidation assay (fluorimetric method). IC 50 values in the low micromolar range were found in four out of five macrocyclic complexes studied, demonstrating their effective ability to scavenge the superoxide anion. The IC 50 values obtained with the NBT assay for the macrocyclic copper(II) complexes, were consistently higher, approximately threefold, than those obtained with the DHE assay. Spectroscopic and electrochemical studies were performed in order to correlate the structural features of the complexes with their superoxide scavenger activity. Cytotoxicity assays were also performed using the MTT method in V79 mammalian cells and we found that the complexes, in the range of concentrations tested in the superoxide scavenging assays were not considerably toxic. In summary, some of the presented macrocyclic copper(II) complexes, specially those with a high stability constant and low IC 50 , appear to be promising superoxide scavenger agents, and should be considered for further biological assays.

Original languageEnglish
Pages (from-to)849-858
Number of pages10
JournalJournal of Inorganic Biochemistry
Volume101
Issue number5
DOIs
Publication statusPublished - 1 May 2007

Fingerprint

Scavenging
Cytotoxicity
Superoxides
Copper
Assays
Xanthine
Xanthine Oxidase
Poisons
Coordination Complexes
Biological Assay
Superoxide Dismutase
Oxidative stress
Oxidative Stress
Ligands
Cells
Pharmaceutical Preparations
Oxidation
dihydroethidium
4-anisyltetrazolium blue

Keywords

  • Antioxidant
  • Copper(II) complexes
  • Macrocycles
  • Superoxide dismutase
  • Superoxide scavenging activity

Cite this

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abstract = "Synthetic superoxide dismutase mimetics have emerged as a potential novel class of drugs for the treatment of oxidative stress related diseases. Among these agents, metal complexes with macrocyclic ligands constitute an important group. In this work we synthesized five macrocyclic copper(II) complexes and evaluated their ability to scavenge the superoxide anions generated by the xanthine-xanthine oxidase system. Two different endpoints were used, the nitro blue tetrazolium (NBT) reduction assay (colorimetric method) and the dihydroethidium (DHE) oxidation assay (fluorimetric method). IC 50 values in the low micromolar range were found in four out of five macrocyclic complexes studied, demonstrating their effective ability to scavenge the superoxide anion. The IC 50 values obtained with the NBT assay for the macrocyclic copper(II) complexes, were consistently higher, approximately threefold, than those obtained with the DHE assay. Spectroscopic and electrochemical studies were performed in order to correlate the structural features of the complexes with their superoxide scavenger activity. Cytotoxicity assays were also performed using the MTT method in V79 mammalian cells and we found that the complexes, in the range of concentrations tested in the superoxide scavenging assays were not considerably toxic. In summary, some of the presented macrocyclic copper(II) complexes, specially those with a high stability constant and low IC 50 , appear to be promising superoxide scavenger agents, and should be considered for further biological assays.",
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Macrocyclic copper(II) complexes : Superoxide scavenging activity, structural studies and cytotoxicity evaluation. / Fernandes, Ana S.; Gaspar, Jorge; Cabral, M. Fátima; Caneiras, Cátia; Guedes, Rita; Rueff, José; Castro, Matilde; Costa, Judite; Oliveira, Nuno G.

In: Journal of Inorganic Biochemistry, Vol. 101, No. 5, 01.05.2007, p. 849-858.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Macrocyclic copper(II) complexes

T2 - Superoxide scavenging activity, structural studies and cytotoxicity evaluation

AU - Fernandes, Ana S.

AU - Gaspar, Jorge

AU - Cabral, M. Fátima

AU - Caneiras, Cátia

AU - Guedes, Rita

AU - Rueff, José

AU - Castro, Matilde

AU - Costa, Judite

AU - Oliveira, Nuno G.

PY - 2007/5/1

Y1 - 2007/5/1

N2 - Synthetic superoxide dismutase mimetics have emerged as a potential novel class of drugs for the treatment of oxidative stress related diseases. Among these agents, metal complexes with macrocyclic ligands constitute an important group. In this work we synthesized five macrocyclic copper(II) complexes and evaluated their ability to scavenge the superoxide anions generated by the xanthine-xanthine oxidase system. Two different endpoints were used, the nitro blue tetrazolium (NBT) reduction assay (colorimetric method) and the dihydroethidium (DHE) oxidation assay (fluorimetric method). IC 50 values in the low micromolar range were found in four out of five macrocyclic complexes studied, demonstrating their effective ability to scavenge the superoxide anion. The IC 50 values obtained with the NBT assay for the macrocyclic copper(II) complexes, were consistently higher, approximately threefold, than those obtained with the DHE assay. Spectroscopic and electrochemical studies were performed in order to correlate the structural features of the complexes with their superoxide scavenger activity. Cytotoxicity assays were also performed using the MTT method in V79 mammalian cells and we found that the complexes, in the range of concentrations tested in the superoxide scavenging assays were not considerably toxic. In summary, some of the presented macrocyclic copper(II) complexes, specially those with a high stability constant and low IC 50 , appear to be promising superoxide scavenger agents, and should be considered for further biological assays.

AB - Synthetic superoxide dismutase mimetics have emerged as a potential novel class of drugs for the treatment of oxidative stress related diseases. Among these agents, metal complexes with macrocyclic ligands constitute an important group. In this work we synthesized five macrocyclic copper(II) complexes and evaluated their ability to scavenge the superoxide anions generated by the xanthine-xanthine oxidase system. Two different endpoints were used, the nitro blue tetrazolium (NBT) reduction assay (colorimetric method) and the dihydroethidium (DHE) oxidation assay (fluorimetric method). IC 50 values in the low micromolar range were found in four out of five macrocyclic complexes studied, demonstrating their effective ability to scavenge the superoxide anion. The IC 50 values obtained with the NBT assay for the macrocyclic copper(II) complexes, were consistently higher, approximately threefold, than those obtained with the DHE assay. Spectroscopic and electrochemical studies were performed in order to correlate the structural features of the complexes with their superoxide scavenger activity. Cytotoxicity assays were also performed using the MTT method in V79 mammalian cells and we found that the complexes, in the range of concentrations tested in the superoxide scavenging assays were not considerably toxic. In summary, some of the presented macrocyclic copper(II) complexes, specially those with a high stability constant and low IC 50 , appear to be promising superoxide scavenger agents, and should be considered for further biological assays.

KW - Antioxidant

KW - Copper(II) complexes

KW - Macrocycles

KW - Superoxide dismutase

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JF - Journal of Inorganic Biochemistry

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