Azobioisosteres of Curcumin with Pronounced Activity against Amyloid Aggregation, Intracellular Oxidative Stress, and Neuroinflammation.
Chemistry
; 27(19): 6015-6027, 2021 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-33666306
ABSTRACT
Many (poly-)phenolic natural products, for example, curcumin and taxifolin, have been studied for their activity against specific hallmarks of neurodegeneration, such as amyloid-ß 42 (Aß42) 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 Aß42, which adopts different folds, affecting the propensity to populate fibril-like conformations. Furthermore, the curcumin bioisosteres exceeded the parent compound in activity against Aß42 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 2.5â
µm (83 % cell survival), whereas curcumin only showed very low protection at 10â
µm (21 % cell survival).
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Curcumina
/
Amiloidosis
Límite:
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article