Azobioisosteres of Curcumin with Pronounced Activity against Amyloid Aggregation, Intracellular Oxidative Stress, and Neuroinflammation.
amyloid beta
bioisosterism
natural products
neuroprotectivity
replica-exchange molecular dynamics
Journal
Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783
Informations de publication
Date de publication:
01 Apr 2021
01 Apr 2021
Historique:
revised:
14
01
2021
received:
09
12
2020
pubmed:
6
3
2021
medline:
7
4
2021
entrez:
5
3
2021
Statut:
ppublish
Résumé
Many (poly-)phenolic natural products, for example, curcumin and taxifolin, have been studied for their activity against specific hallmarks of neurodegeneration, such as amyloid-β 42 (Aβ42) aggregation and neuroinflammation. Due to their drawbacks, arising from poor pharmacokinetics, rapid metabolism, and even instability in aqueous medium, the biological activity of azobenzene compounds carrying a pharmacophoric catechol group, which have been designed as bioisoteres of curcumin has been examined. Molecular simulations reveal the ability of these compounds to form a hydrophobic cluster with Aβ42, which adopts different folds, affecting the propensity to populate fibril-like conformations. Furthermore, the curcumin bioisosteres exceeded the parent compound in activity against Aβ42 aggregation inhibition, glutamate-induced intracellular oxidative stress in HT22 cells, and neuroinflammation in microglial BV-2 cells. The most active compound prevented apoptosis of HT22 cells at a concentration of 2.5 μm (83 % cell survival), whereas curcumin only showed very low protection at 10 μm (21 % cell survival).
Identifiants
pubmed: 33666306
doi: 10.1002/chem.202005263
pmc: PMC8048673
doi:
Substances chimiques
Amyloid
0
Amyloid beta-Peptides
0
Curcumin
IT942ZTH98
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6015-6027Subventions
Organisme : European Cooperation in Science and Technology
ID : MuTaLig
Organisme : German Excellence Initiative
ID : Graduate School of Life Sciences, University of Würzburg
Organisme : Generalitat de Catalunya
ID : 2017SGR1746; 2019LLAV00016
Organisme : Spanish Ministerio de Economía y Competitividad
ID : MDM2017-0767; AEI/FEDER UE
Informations de copyright
© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.
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