Novel Cu II quinoxaline N1,N4-dioxide complexes as selective hypoxic cytotoxins.

COBRE

COMPLEJOS

CITOTOXINAS

BIBLIOGRAFIA NACIONAL QUIMICA

2005

As an effort to develop novel selective hypoxia-cytotoxins and to improve bioavailability and pharmacological and toxicological properties of quinoxaline N1,N4-dioxide derivatives (L1 = 3-amino-6(7)-chloroquinoxaline-2-carbonitrile N1,N4-dioxide, L2 = 3-amino-6(7)- bromoquinoxaline-2-carbonitrile N1,N4-dioxide and L3 = 3-amino-6(7)-methylquinoxaline-2-carbonitrile N1,N4-dioxide) and to get a synergism among metals and these type of bioreductive agents, L2 and three novel Cu(II) complexes of general formulae [CuII(H2O)x(L – H)2], where L = L1 (x = 1), L2 (x = 0) or L3 (x = 2) were developed. L2 and complexes were synthesized and structurally characterized by elemental and thermal analyses, and FTIR, electronic, MS, NMR, and EPR spectroscopies. The new compounds were subjected to cytotoxic evaluation in V79 cells in hypoxic and aerobic conditions. The complexes showed excellent selective cytotoxicity in hypoxia, being their cytotoxicity similar to or higher than that of the ligands L1–L3. Besides, the copper complexes were so poorly cytotoxic in oxia as the free ligands. In addition, for the first time Cu(II)-quinoxaline complexes are reported as a family of hypoxic cytotoxins.

European Journal of Medicinal Chemistry v. 40, no. 5, 2005. -- p. 473-480

Elsevier

2005

As an effort to develop novel selective hypoxia-cytotoxins and to improve bioavailability and pharmacological and toxicological properties
of quinoxaline N1,N4-dioxide derivatives (L1 = 3-amino-6(7)-chloroquinoxaline-2-carbonitrile N1,N4-dioxide, L2 = 3-amino-6(7)-
bromoquinoxaline-2-carbonitrile N1,N4-dioxide and L3 = 3-amino-6(7)-methylquinoxaline-2-carbonitrile N1,N4-dioxide) and to get a synergism
among metals and these type of bioreductive agents, L2 and three novel Cu(II) complexes of general formulae [CuII(H2O)x(L – H)2],
where L = L1 (x = 1), L2 (x = 0) or L3 (x = 2) were developed. L2 and complexes were synthesized and structurally characterized by elemental
and thermal analyses, and FTIR, electronic, MS, NMR, and EPR spectroscopies. The new compounds were subjected to cytotoxic evaluation
in V79 cells in hypoxic and aerobic conditions. The complexes showed excellent selective cytotoxicity in hypoxia, being their cytotoxicity
similar to or higher than that of the ligands L1–L3. Besides, the copper complexes were so poorly cytotoxic in oxia as the free ligands. In
addition, for the first time Cu(II)-quinoxaline complexes are reported as a family of hypoxic cytotoxins.

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Inglés

Artículo

doi:10.1016/j.ejmech.2004.11.012

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