Novel dual inhibitors of calpain and lipid peroxidation.
A series of molecules with dual inhibitory activities on calpain and lipid peroxidation were synthesized. These hybrid compounds were built on the calpain pharmacophore 2-hydroxytetrahydrofuran linked to a set of antioxidants via a l-leucine linker. Compound 7, the most potent in cellular calpain and lipid peroxidation inhibitions, provided effective protection against glial cell death induced by maitotoxin.
Auvin
Serge
S
Department of Medicinal Chemistry, Ipsen Research Laboratories, Institut Henri Beaufour, 5, Avenue du Canada, 91966 Les Ulis Cedex, France. serge.auvin@ipsen.com
Pignol
Bernadette
B
Navet
Edith
E
Pons
Dominique
D
Marin
Jean-G
JG
Bigg
Dennis
D
Chabrier
Pierre-E
PE
D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D005663:Furans / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007930:Leucine / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D009457:Neuroglia; D013329:Structure-Activity Relationship
D000975:Antioxidants; D005663:Furans; D016859:Lipoxygenase Inhibitors; D002154:Calpain; D007930:Leucine