Conjugates of desferrioxamine and aromatic amines improve markers of iron-dependent neurotoxicity

Rodrigo R.V. Carvalho; Tanara V. Peres; Cleber W. Liria; M. Teresa Machini; Michael Aschner; Breno P. Espósito

doi:10.1007/s10534-020-00277-7

Conjugates of desferrioxamine and aromatic amines improve markers of iron-dependent neurotoxicity

Rodrigo R.V. Carvalho, Tanara V. Peres, Cleber W. Liria, M. Teresa Machini, Michael Aschner, Breno P. Espósito

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

4 Scopus citations

Abstract

Abstract: Alzheimer’s Disease (AD) is a complex neurodegenerative disorder associated in some instances with dyshomeostasis of redox-active metal ions, such as copper and iron. In this work, we investigated whether the conjugation of various aromatic amines would improve the pharmacological efficacy of the iron chelator desferrioxamine (DFO). Conjugates of DFO with aniline (DFOANI), benzosulfanylamide (DFOBAN), 2-naphthalenamine (DFONAF) and 6-quinolinamine (DFOQUN) were obtained and their properties examined. DFOQUN had good chelating activity, promoted a significant increase in the inhibition of β-amyloid peptide aggregation when compared to DFO, and also inhibited acetylcholinesterase (AChE) activity both in vitro and in vivo (Caenorhabditis elegans). These data indicate that the covalent conjugation of a strong iron chelator to an AChE inhibitor offers a powerful approach for the amelioration of iron-induced neurotoxicity symptoms. Graphic abstract: [Figure not available: see fulltext.]

Original language	English
Pages (from-to)	259-275
Number of pages	17
Journal	BioMetals
Volume	34
Issue number	2
DOIs	https://doi.org/10.1007/s10534-020-00277-7
State	Published - Apr 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.

Keywords

Acetylcholinesterase
Alzheimer’s disease
Beta amyloid
Caenorhabditis elegans
Desferrioxamine
Iron

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10.1007/s10534-020-00277-7

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title = "Conjugates of desferrioxamine and aromatic amines improve markers of iron-dependent neurotoxicity",

abstract = "Abstract: Alzheimer{\textquoteright}s Disease (AD) is a complex neurodegenerative disorder associated in some instances with dyshomeostasis of redox-active metal ions, such as copper and iron. In this work, we investigated whether the conjugation of various aromatic amines would improve the pharmacological efficacy of the iron chelator desferrioxamine (DFO). Conjugates of DFO with aniline (DFOANI), benzosulfanylamide (DFOBAN), 2-naphthalenamine (DFONAF) and 6-quinolinamine (DFOQUN) were obtained and their properties examined. DFOQUN had good chelating activity, promoted a significant increase in the inhibition of β-amyloid peptide aggregation when compared to DFO, and also inhibited acetylcholinesterase (AChE) activity both in vitro and in vivo (Caenorhabditis elegans). These data indicate that the covalent conjugation of a strong iron chelator to an AChE inhibitor offers a powerful approach for the amelioration of iron-induced neurotoxicity symptoms. Graphic abstract: [Figure not available: see fulltext.]",

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AU - Carvalho, Rodrigo R.V.

AU - Peres, Tanara V.

AU - Liria, Cleber W.

AU - Machini, M. Teresa

AU - Aschner, Michael

AU - Espósito, Breno P.

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N2 - Abstract: Alzheimer’s Disease (AD) is a complex neurodegenerative disorder associated in some instances with dyshomeostasis of redox-active metal ions, such as copper and iron. In this work, we investigated whether the conjugation of various aromatic amines would improve the pharmacological efficacy of the iron chelator desferrioxamine (DFO). Conjugates of DFO with aniline (DFOANI), benzosulfanylamide (DFOBAN), 2-naphthalenamine (DFONAF) and 6-quinolinamine (DFOQUN) were obtained and their properties examined. DFOQUN had good chelating activity, promoted a significant increase in the inhibition of β-amyloid peptide aggregation when compared to DFO, and also inhibited acetylcholinesterase (AChE) activity both in vitro and in vivo (Caenorhabditis elegans). These data indicate that the covalent conjugation of a strong iron chelator to an AChE inhibitor offers a powerful approach for the amelioration of iron-induced neurotoxicity symptoms. Graphic abstract: [Figure not available: see fulltext.]

AB - Abstract: Alzheimer’s Disease (AD) is a complex neurodegenerative disorder associated in some instances with dyshomeostasis of redox-active metal ions, such as copper and iron. In this work, we investigated whether the conjugation of various aromatic amines would improve the pharmacological efficacy of the iron chelator desferrioxamine (DFO). Conjugates of DFO with aniline (DFOANI), benzosulfanylamide (DFOBAN), 2-naphthalenamine (DFONAF) and 6-quinolinamine (DFOQUN) were obtained and their properties examined. DFOQUN had good chelating activity, promoted a significant increase in the inhibition of β-amyloid peptide aggregation when compared to DFO, and also inhibited acetylcholinesterase (AChE) activity both in vitro and in vivo (Caenorhabditis elegans). These data indicate that the covalent conjugation of a strong iron chelator to an AChE inhibitor offers a powerful approach for the amelioration of iron-induced neurotoxicity symptoms. Graphic abstract: [Figure not available: see fulltext.]

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Conjugates of desferrioxamine and aromatic amines improve markers of iron-dependent neurotoxicity

Abstract

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