title: New copper-based complexes with quinoxaline N1,N4-dioxide derivatives, potential antitumoral agents.
abstract: Taking into account our previous studies on cytotoxic metal compounds, new copper complexes with 3-aminoquinoxaline-2-carbonitrile N1,N4-dioxide derivatives as ligands were synthesized and characterized by different spectroscopic methods. The hypoxic selective cytotoxicity towards V79 cells and the superoxide dismutase-like activity of the complexes were determined and related to physicochemical properties of the compounds. In particular, the copper(II) complex with 3-amino-6-chloro-7-fluoroquinoxaline-2-carbonitrile N1,N4-dioxide showed cytotoxic selectivity in hypoxia being the most lipophilic compound of the series. On the contrary, the complex with 3-aminoquinoxaline-2-carbonitrile N1,N4-dioxide was cytotoxic but not selective and that with 3-amino-7-chloro-6-methoxy-quinoxaline-2-carbonitrile N1,N4-dioxide was not cytotoxic towards V79 cells neither in oxia nor in hypoxia in the assayed conditions. The sigmam Hammett substituent electronic descriptor was related to the effect in hypoxic conditions and the SOD-like activity was correlated to the effect in normoxia.
authors.affiliation: Cátedra de Química Inorgánica, Facultad de Química, Universidad de la República, Gral Flores 2124, C.C. 1157, 11800 Montevideo, Uruguay.
authors.forename: Carolina
authors.initials: C
authors.lastname: Urquiola
authors.forename: Dinorah
authors.initials: D
authors.lastname: Gambino
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cabrera
authors.forename: María Laura
authors.initials: ML
authors.lastname: Lavaggi
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
authors.forename: Adela López
authors.initials: AL
authors.lastname: de Cerain
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Costa-Filho
authors.forename: María H
authors.initials: MH
authors.lastname: Torre
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D000860:Hypoxia / Q000503:physiopathology; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D013482:Superoxide Dismutase / Q000378:metabolism