title: Development of pyridine-containing macrocyclic copper(II) complexes: potential role in the redox modulation of oxaliplatin toxicity in human breast cells.
abstract: The unique redox and catalytic chemistry of Cu has justified the development of novel Cu complexes for different therapeutic uses including cancer therapy. In this work, four pyridine-containing aza-macrocyclic copper(II) complexes were prepared (CuL1-CuL4) varying in ring size and/or substituents and their superoxide scavenging activity evaluated. CuL3, the most active superoxide scavenger, was further studied as a modulator of the cytotoxicity of oxaliplatin in epithelial breast MCF10A cells and in MCF7 breast cancer cells. Our results show that CuL3 enhances the therapeutic window of oxaliplatin, by both protecting non-tumour cells and increasing its cytotoxic effect in breast carcinoma cells. CuL3 is thus a promising complex to be further studied and to be used as a lead compound for the optimization of novel chemotherapy sensitizers.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Fernandes
authors.forename: Judite
authors.initials: J
authors.lastname: Costa
authors.forename: Jorge
authors.initials: J
authors.lastname: Gaspar
authors.forename: José
authors.initials: J
authors.lastname: Rueff
authors.forename: M Fátima
authors.initials: MF
authors.lastname: Cabral
authors.forename: Madalena
authors.initials: M
authors.lastname: Cipriano
authors.forename: Matilde
authors.initials: M
authors.lastname: Castro
authors.forename: Nuno G
authors.initials: NG
authors.lastname: Oliveira
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000378:metabolism; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D000077150:Oxaliplatin; D010084:Oxidation-Reduction; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D047028:Macrocyclic Compounds; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; D011725:Pyridines; D000077150:Oxaliplatin; D013481:Superoxides; D017665:Hydroxyl Radical; D003300:Copper; C023666:pyridine