Amphetamine-like Deferiprone and Clioquinol Derivatives as Iron Chelating Agents.

El Safadi, M; Wilson, KA; Strudwicke, IJ; O'Mara, ML; Bhadbhade, M; Rawling, T; McDonagh, AM

Amphetamine-like Deferiprone and Clioquinol Derivatives as Iron Chelating Agents.

El Safadi, M Wilson, KA Strudwicke, IJ O'Mara, ML Bhadbhade, M Rawling, T

McDonagh, AM

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Publisher:: MDPI
Publication Type:: Journal Article
Citation:: Molecules, 2024, 29, (17), pp. 4213
Issue Date:: 2024-09-05

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Field	Value	Language
dc.contributor.author	El Safadi, M
dc.contributor.author	Wilson, KA
dc.contributor.author	Strudwicke, IJ
dc.contributor.author	O'Mara, ML
dc.contributor.author	Bhadbhade, M
dc.contributor.author	Rawling, T https://orcid.org/0000-0002-6624-6586
dc.contributor.author	McDonagh, AM
dc.date.accessioned	2024-11-22T00:39:25Z
dc.date.available	2024-08-31
dc.date.available	2024-11-22T00:39:25Z
dc.date.issued	2024-09-05
dc.identifier.citation	Molecules, 2024, 29, (17), pp. 4213
dc.identifier.issn	1420-3049
dc.identifier.issn	1420-3049
dc.identifier.uri	http://hdl.handle.net/10453/182046
dc.description.abstract	The accumulation of iron in dopaminergic neurons can cause oxidative stress and dopaminergic neuron degeneration. Iron chelation therapy may reduce dopaminergic neurodegeneration, but chelators should be targeted towards dopaminergic cells. In this work, two series of compounds based on 8-hydroxyquinoline and deferiprone, iron chelators that have amphetamine-like structures, have been designed, synthesized and characterized. Each of these compounds chelated iron ions in aqueous solution. The hydroxyquinoline-based compounds exhibited stronger iron-binding constants than those of the deferiprone derivatives. The hydroxyquinoline-based compounds also exhibited greater free radical scavenging activities compared to the deferiprone derivatives. Molecular dynamics simulations showed that the hydroxyquinoline-based compounds generally bound well within human dopamine transporter cavities. Thus, these compounds are excellent candidates for future exploration as drugs against diseases that are affected by iron-induced dopaminergic neuron damage, such as Parkinson's disease.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI
dc.relation.ispartof	Molecules
dc.relation.isbasedon	10.3390/molecules29174213
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 0307 Theoretical and Computational Chemistry
dc.subject.classification	Organic Chemistry
dc.subject.classification	3404 Medicinal and biomolecular chemistry
dc.subject.classification	3405 Organic chemistry
dc.subject.mesh	Deferiprone
dc.subject.mesh	Iron Chelating Agents
dc.subject.mesh	Humans
dc.subject.mesh	Iron
dc.subject.mesh	Clioquinol
dc.subject.mesh	Molecular Dynamics Simulation
dc.subject.mesh	Dopamine Plasma Membrane Transport Proteins
dc.subject.mesh	Free Radical Scavengers
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Amphetamine
dc.subject.mesh	Humans
dc.subject.mesh	Iron
dc.subject.mesh	Amphetamine
dc.subject.mesh	Clioquinol
dc.subject.mesh	Iron Chelating Agents
dc.subject.mesh	Free Radical Scavengers
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Dopamine Plasma Membrane Transport Proteins
dc.subject.mesh	Molecular Dynamics Simulation
dc.subject.mesh	Deferiprone
dc.title	Amphetamine-like Deferiprone and Clioquinol Derivatives as Iron Chelating Agents.
dc.type	Journal Article
utslib.citation.volume	29
utslib.location.activity	Switzerland
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0305 Organic Chemistry
utslib.for	0307 Theoretical and Computational Chemistry
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Clean Energy Technology (CCET)
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2024-11-22T00:39:24Z
pubs.issue	17
pubs.publication-status	Published online
pubs.volume	29
utslib.citation.issue	17

Abstract:

The accumulation of iron in dopaminergic neurons can cause oxidative stress and dopaminergic neuron degeneration. Iron chelation therapy may reduce dopaminergic neurodegeneration, but chelators should be targeted towards dopaminergic cells. In this work, two series of compounds based on 8-hydroxyquinoline and deferiprone, iron chelators that have amphetamine-like structures, have been designed, synthesized and characterized. Each of these compounds chelated iron ions in aqueous solution. The hydroxyquinoline-based compounds exhibited stronger iron-binding constants than those of the deferiprone derivatives. The hydroxyquinoline-based compounds also exhibited greater free radical scavenging activities compared to the deferiprone derivatives. Molecular dynamics simulations showed that the hydroxyquinoline-based compounds generally bound well within human dopamine transporter cavities. Thus, these compounds are excellent candidates for future exploration as drugs against diseases that are affected by iron-induced dopaminergic neuron damage, such as Parkinson's disease.

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http://hdl.handle.net/10453/182046