%0 Journal Article %1 https://doi.org/10.1002/chem.202005263 %A Hofmann, Julian %A Ginex, Tiziana %A Espargaró, Alba %A Scheiner, Matthias %A Gunesch, Sandra %A Aragó, Marc %A Stigloher, Christian %A Sabaté, Raimon %A Luque, F. Javier %A Decker, Michael %D 2021 %J Chemistry – A European Journal %K extern myown %N 19 %P 6015-6027 %R https://doi.org/10.1002/chem.202005263 %T Azobioisosteres of Curcumin with Pronounced Activity against Amyloid Aggregation, Intracellular Oxidative Stress, and Neuroinflammation %U https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202005263 %V 27 %X 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-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).

@article{https://doi.org/10.1002/chem.202005263, abstract = {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-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).}, added-at = {2021-11-11T13:11:26.000+0100}, author = {Hofmann, Julian and Ginex, Tiziana and Espargaró, Alba and Scheiner, Matthias and Gunesch, Sandra and Aragó, Marc and Stigloher, Christian and Sabaté, Raimon and Luque, F. Javier and Decker, Michael}, biburl = {https://www.bibsonomy.org/bibtex/2e49e00dc11bb8ee78880e4c11dd053dd/zam}, doi = {https://doi.org/10.1002/chem.202005263}, eprint = {https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/chem.202005263}, interhash = {5bcd627f8540250e88cc69ce0f11d65d}, intrahash = {e49e00dc11bb8ee78880e4c11dd053dd}, journal = {Chemistry – A European Journal}, keywords = {extern myown}, number = 19, pages = {6015-6027}, timestamp = {2021-11-11T13:11:26.000+0100}, title = {Azobioisosteres of Curcumin with Pronounced Activity against Amyloid Aggregation, Intracellular Oxidative Stress, and Neuroinflammation}, url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202005263}, volume = 27, year = 2021 }