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

Hailin Zheng; Lev M. Weiner; Orit Bar-Am; Silvina Epsztejn; Z. Ioav Cabantchik; Abraham Warshawsky; Moussa B.H. Youdim; Mati Fridkin

doi:10.1016/j.bmc.2004.10.037

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

Hailin Zheng
, Lev M. Weiner
, Orit Bar-Am
, Silvina Epsztejn
, Z. Ioav Cabantchik
, Abraham Warshawsky
, Moussa B.H. Youdim
, Mati Fridkin

Alexander Silberman Institute of Life Sciences

Research output: Contribution to journal › Article › peer-review

286 Scopus citations

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 (IC ₅₀ 110 μM), 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.

Original language	English
Pages (from-to)	773-783
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	13
Issue number	3
DOIs	https://doi.org/10.1016/j.bmc.2004.10.037
State	Published - 1 Feb 2005

Keywords

8-Hydroxyquinoline
Antioxidant-iron chelator
Lipid peroxidation
Neuroprotection

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10.1016/j.bmc.2004.10.037

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Zheng, H., Weiner, L. M., Bar-Am, O., Epsztejn, S., Cabantchik, Z. I., Warshawsky, A., Youdim, M. B. H., & Fridkin, M. (2005). Design, synthesis, and evaluation of novel bifunctional iron-chelators as potential agents for neuroprotection in Alzheimer's, Parkinson's, and other neurodegenerative diseases. Bioorganic and Medicinal Chemistry, 13(3), 773-783. https://doi.org/10.1016/j.bmc.2004.10.037

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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 (IC 50 110 μM), 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.",

keywords = "8-Hydroxyquinoline, Antioxidant-iron chelator, Lipid peroxidation, Neuroprotection",

author = "Hailin Zheng and Weiner, \{Lev M.\} and Orit Bar-Am and Silvina Epsztejn and Cabantchik, \{Z. Ioav\} and Abraham Warshawsky and Youdim, \{Moussa B.H.\} and Mati Fridkin",

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doi = "10.1016/j.bmc.2004.10.037",

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Zheng, H, Weiner, LM, Bar-Am, O, Epsztejn, S, Cabantchik, ZI, Warshawsky, A, Youdim, MBH & Fridkin, M 2005, 'Design, synthesis, and evaluation of novel bifunctional iron-chelators as potential agents for neuroprotection in Alzheimer's, Parkinson's, and other neurodegenerative diseases', Bioorganic and Medicinal Chemistry, vol. 13, no. 3, pp. 773-783. https://doi.org/10.1016/j.bmc.2004.10.037

Design, synthesis, and evaluation of novel bifunctional iron-chelators as potential agents for neuroprotection in Alzheimer's, Parkinson's, and other neurodegenerative diseases. / Zheng, Hailin; Weiner, Lev M.; Bar-Am, Orit et al.
In: Bioorganic and Medicinal Chemistry, Vol. 13, No. 3, 01.02.2005, p. 773-783.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Design, synthesis, and evaluation of novel bifunctional iron-chelators as potential agents for neuroprotection in Alzheimer's, Parkinson's, and other neurodegenerative diseases

AU - Zheng, Hailin

AU - Weiner, Lev M.

AU - Bar-Am, Orit

AU - Epsztejn, Silvina

AU - Cabantchik, Z. Ioav

AU - Warshawsky, Abraham

AU - Youdim, Moussa B.H.

AU - Fridkin, Mati

PY - 2005/2/1

Y1 - 2005/2/1

N2 - 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 (IC 50 110 μM), 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.

AB - 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 (IC 50 110 μM), 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.

KW - 8-Hydroxyquinoline

KW - Antioxidant-iron chelator

KW - Lipid peroxidation

KW - Neuroprotection

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AN - SCOPUS:11844255676

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JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 3

ER -

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

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Keywords

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