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.
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Acknowledgements
This work was supported by FAPESP (2016/03709-9 and 2018/19684-0 to BPE and 2015/14360-4 to MTM) and CAPES (Brazilian agencies). MA was supported in part by grants from the National Institute of Environmental Health Science (NIEHS) R01ES07331 and R01ES10563.
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FAPESP 15/14360-4, 16/03709-9 and 18/19684-0; CAPES 88881.131918/2016-01; NIEHS R01ES07331 and R01ES10563.
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Carvalho, R.R.V., Peres, T.V., Liria, C.W. et al. Conjugates of desferrioxamine and aromatic amines improve markers of iron-dependent neurotoxicity. Biometals 34, 259–275 (2021). https://doi.org/10.1007/s10534-020-00277-7
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DOI: https://doi.org/10.1007/s10534-020-00277-7