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.