title: Design, synthesis, and evaluation of novel bifunctional iron-chelators as potential agents for neuroprotection in Alzheimer's, Parkinson's, and other neurodegenerative diseases.
abstract: Several novel antioxidant-iron chelators bearing 8-hydroxyoxyquinoline moiety were synthesized, and various properties related to their iron chelation, and neuroprotective action were investigated. All the chelators exhibited strong iron(III) chelating and high antioxidant properties. Chelator 9 (HLA20), having good permeability into K562 cells and moderate selective MAO-B inhibitory activity (IC50 110 microM), displayed the hightest protective effects against differentiated P19 cell death induced by 6-hydroxydopamine. EPR studies suggested that Chelator 9 also act as radical scavenger to directly scavenge hydroxyl radical.
authors.affiliation: Department of Organic Chemistry and Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Hailin
authors.initials: H
authors.lastname: Zheng
authors.forename: Lev M
authors.initials: LM
authors.lastname: Weiner
authors.forename: Orit
authors.initials: O
authors.lastname: Bar-Am
authors.forename: Silvina
authors.initials: S
authors.lastname: Epsztejn
authors.forename: Z Ioav
authors.initials: ZI
authors.lastname: Cabantchik
authors.forename: Abraham
authors.initials: A
authors.lastname: Warshawsky
authors.forename: Moussa B H
authors.initials: MB
authors.lastname: Youdim
authors.forename: Mati
authors.initials: M
authors.lastname: Fridkin
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007502:Iron Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D020014:K562 Cells; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents