Design, synthesis, and evaluation of novel bifunctional iron-chelators as potential agents for neuroprotection in Alzheimer's, Parkinson's, and other neurodegenerative diseases.
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.
Zheng
Hailin
H
Department of Organic Chemistry and Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Weiner
Lev M
LM
Bar-Am
Orit
O
Epsztejn
Silvina
S
Cabantchik
Z Ioav
ZI
Warshawsky
Abraham
A
Youdim
Moussa B H
MB
Fridkin
Mati
M
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*
D000975:Antioxidants; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents