1,1'-Xylyl bis-1,4,8,11-tetraaza cyclotetradecane: a new potential copper chelator agent for neuroprotection in Alzheimer's disease. Its comparative effects with clioquinol on rat brain copper distribution.
Dysfunction of copper metabolism leading to its excess or deficiency results in severe ailments. Recently, neurodegenerative disorders such as Alzheimer's disease have been associated with copper metabolism. Compounds having the ability to reduce copper levels in brain or to affect its distribution could have neuroprotective effects, mainly through a downregulation of the transcription of amyloid peptide precursor (APP). We report here the biological effect of compound 1,1'-xylyl bis-1,4,8,11-tetraaza cyclotetradecane, which specifically affects copper concentration in the brain cortex region. Its copper homeostatic activity is compared with that of clioquinol, a well-known drug, which has been recently reported as an active A beta-peptide clearance drug in vivo for Alzheimer's patients.
INSERM U-623, IBDM, Laboratoire de Chimie Biomoléculaire, Faculté des Sciences de Luminy, Université de la Méditerranée, 13288 Marseille Cedex 9, France.
Vincent
V
Moret
Younes
Y
Laras
Nicolas
N
Pietrancosta
Cédrik
C
Garino
Gilles
G
Quéléver
Amandine
A
Rolland
Bernard
B
Mallet
Jean-Chrétien
JC
Norreel
Jean-Louis
JL
Kraus
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D002614:Chelating Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D007464:Clioquinol / Q000493:pharmacokinetics*; D003300:Copper / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship
C512302:1,1'-xylyl bis-1,4,8,11-tetraaza cyclotetradecane; D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D003300:Copper; D007464:Clioquinol