Design, synthesis, and evaluation of novel bifunctional iron-chelators as potential agents for neuroprotection in Alzheimer's, Parkinson's, and other neurodegenerative diseases

  • Bioorg Med Chem. 2005 Feb 1;13(3):773-83. doi: 10.1016/j.bmc.2004.10.037.
Hailin Zheng  1 ,  Lev M Weiner ,  Orit Bar-Am ,  Silvina Epsztejn ,  Z Ioav Cabantchik ,  Abraham Warshawsky ,  Moussa B H Youdim ,  Mati Fridkin
Affiliations
  • 1. Department of Organic Chemistry and Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
PMID: 15653345 DOI: 10.1016/j.bmc.2004.10.037
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.

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