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AssigneesYeda Research and Development Co. Ltd., Technion Research & Development Foundation Limited
InventorsMOUSSA YOUDIM, Matitiyahu Fridkin, Hailin Zheng, Abraham Warshawsky, Rivka Warshawsky
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Novel iron chelators exhibiting neuroprotective and good transport properties are useful in iron chelation therapy for treatment of a disease, disorder or condition associated with iron overload and oxidative stress, e.g., a neurodegenerative or cerebrovascular disease or disorder, a neoplastic disease, hemochromatosis, thalassemia, a cardiovascular disease, diabetes, an inflammatory disorder, anthracycline cardiotoxicity, a viral infection, a protozoal infection, a yeast infection, retarding aging, and prevention and/or treatment of skin aging and skin protection against sunlight and/or UV light. The iron chelator function is provided by a 8-hydroxyquinoline, a hydroxypyridinone or a hydroxamate moiety. The neuroprotective function is imparted to the compound, e.g., by a neuroprotective peptide. A combined antiapoptotic and neuroprotective function is provided by a propargyl group.
A method for treatment of a neurodegenerative or cerebrovascular disease, condition or disorder, which comprises administering to an individual in need thereof an effective amount of a compound comprising a moiety having an iron chelator function, said iron chelating moiety being selected from the group consisting of an 8-hydroxyquinoline moiety, a hydroxamate moiety, and a pyridinone moiety, and, in addition, one or both of the following moieties:
The method according to claim 7 wherein said neuroprotective peptide is vasoactive intestinal peptide (VIP), gonadotropin-releasing hormone (GnRH), Substance P or enkephalin, and said analog of neuroprotective peptide or neuroprotective peptide fragment is an analog of VIP, GnRH, Substance P or enkephalin or of a fragment thereof, in which one amino acid residue is replaced by a L- or D-cysteine residue.
The method according to claim 8, wherein said analog is selected from the group consisting of the VIP fragment analogs of SEQ ID NO:2 that may bear a stearyl or a Fmoc group at the amino terminal, the GnRH analogs of SEQ ID NO:4 and SEQ ID NO:5, the Substance P analogs of SEQ ID NO:7 and SEQ ID NO:8, and the enkephalin analogs of SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:14.
Dependencies are inferred from the claim text.