TY  - JOUR
A1  - Hofmann, Julian
A1  - Ginex, Tiziana
A1  - Espargaró, Alba
A1  - Scheiner, Matthias
A1  - Gunesch, Sandra
A1  - Aragó, Marc
A1  - Stigloher, Christian
A1  - Sabaté, Raimon
A1  - Luque, F. Javier
A1  - Decker, Michael
T1  - Azobioisosteres of Curcumin with Pronounced Activity against Amyloid Aggregation, Intracellular Oxidative Stress, and Neuroinflammation
T2  - Chemistry – A European Journal
N2  - 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).
KW  - amyloid beta
KW  - bioisosterism
KW  - natural products
KW  - neuroprotectivity
KW  - replica-exchange molecular dynamics
Y1  - 2021
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/23898
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-238988
VL  - 27
IS  - 19
SP  - 6015
EP  - 6027
ER  -