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
JF  - 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
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238988
VL  - 27
IS  - 19
SP  - 6015
EP  - 6027
ER  - 
TY  - THES
A1  - Daiß, Jürgen Oliver
T1  - Synthesis of sila-analogs and silicon-containing derivatives of drugs and development and application of the Si-2,4,6-trimethoxyphenyl moiety as a novel protecting group in organosilicon chemistry
T1  - Synthese von Sila-Analoga und siliciumhaltigen Derivaten von Wirkstoffen und Entwicklung und Anwendung der Si-2,4,6-Trimethoxyphenyl-Gruppe als neuartige Schutzgruppe in der Organosilicium-Chemie
N2  - The present work describes the synthesis of sila-venlafaxine, disila-bexarotene, disila-AG-045572 (disila-CMPD1), a series of silicon-based allosteric modulators of muscarinic receptors, and a partial synthesis of sila-gabapentin. Crystal structure data of rac-sila-venlafaxine hydrochloride, (R)-sila-venlafaxine hydrobromide, bexarotene, disila-bexarotene, and disila-AG-045572 (disila-CMPD1) are included. Studies on the biological activities of sila-venlafaxine and of silicon-based allosteric modulators of muscarinic receptors are discussed. The Si-2,4,6-trimethoxyphenyl (Si-2,4,6-TMOP) moiety is described as a novel, acid-labile protecting group in organosilicon chemistry. The synthesis of chlorotris(chloromethyl)silane and tris(chloromethyl)methoxysilane is described.
N2  - Die vorliegende Arbeit beschreibt die Synthese von Sila-Venlafaxin, Disila-Bexaroten, Disila-AG-045572 (Disila-CMPD1), einer Reihe allosterer Modulatoren von Muscarin-Rezeptoren auf Silicium-Basis sowie eine Teilsynthese von Sila-Gabapentin. Kristallstrukturdaten von rac-Sila-Venlafaxin Hydrochlorid, (R)-Sila-Venlafaxin Hydrobromid, Bexaroten, Disila-Bexaroten und Disila-AG-045572 (Disila-CMPD1) sind enthalten. Untersuchungen der biologischen Aktivität von Sila-Venlafaxin und allosterer Modulatoren von Muscarin-Rezeptoren auf Silicium-Basis werden diskutiert. Die Si-2,4,6-trimethoxyphenyl-Gruppe (Si-2,4,6-TMOP)wird als neuartige säurelabile Scutzgruppe für die Organosilicium-Chemie beschrieben. Die Synthese von Chlortris(chlormethyl)silan und Tris(chlormethyl)methoxysilan wird ebenfalls beschrieben.
KW  - Wirkstoff
KW  - Siliciumorganische Verbindungen
KW  - Bioisosterie
KW  - Muscarin
KW  - Antagonist
KW  - Silicium
KW  - Bioisosterie
KW  - Schutzgruppe
KW  - Venlafaxin
KW  - Bexaroten
KW  - Silicon
KW  - bioisosterism
KW  - protecting group
KW  - venlafaxine
KW  - bexarotene
Y1  - 2004
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-11187
ER  -