New copper-based complexes with quinoxaline N1,N4-dioxide derivatives, potential antitumoral agents.
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.
Urquiola
Carolina
C
Cátedra de Química Inorgánica, Facultad de Química, Universidad de la República, Gral Flores 2124, C.C. 1157, 11800 Montevideo, Uruguay.
Gambino
Dinorah
D
Cabrera
Mauricio
M
Lavaggi
María Laura
ML
Cerecetto
Hugo
H
González
Mercedes
M
de Cerain
Adela López
AL
Monge
Antonio
A
Costa-Filho
Antonio J
AJ
Torre
María H
MH
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