TY  - JOUR
A1  - Sawatzky, Edgar
A1  - Drakopoulos, Antonios
A1  - Rölz, Martin
A1  - Sotriffer, Christoph
A1  - Engels, Bernd
A1  - Decker, Michael
T1  - Experimental and theoretical investigations into the stability of cyclic aminals
JF  - Beilstein Journal of Organic Chemistry
N2  - Background: Cyclic aminals are core features of natural products, drug molecules and important synthetic intermediates. Despite their relevance, systematic investigations into their stability towards hydrolysis depending on the pH value are lacking.

Results: A set of cyclic aminals was synthesized and their stability quantified by kinetic measurements. Steric and electronic effects were investigated by choosing appropriate groups. Both molecular mechanics (MM) and density functional theory (DFT) based studies were applied to support and explain the results obtained. Rapid decomposition is observed in acidic aqueous media for all cyclic aminals which occurs as a reversible reaction. Electronic effects do not seem relevant with regard to stability, but the magnitude of the conformational energy of the ring system and pK a values of the N-3 nitrogen atom.

Conclusion: Cyclic aminals are stable compounds when not exposed to acidic media and their stability is mainly dependent on the conformational energy of the ring system. Therefore, for the preparation and work-up of these valuable synthetic intermediates and natural products, appropriate conditions have to be chosen and for application as drug molecules their sensitivity towards hydrolysis has to be taken into account.
KW  - quantum mechanics
KW  - hydrolysis
KW  - kinetics
KW  - molecular mechanics
KW  - natural products
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160976
VL  - 12
ER  - 
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  - Glaser, Jan
T1  - Antileishmanial compounds from Nature - Elucidation of the active principles of an extract from Valeriana wallichii rhizomes
T1  - Antileishmaniale Wirkstoffe aus der Natur - Aufklärung des Wirkprinzips eines Wurzelextraktes von Valeriana wallichii
N2  - This study is dealing with the bioactivity-guided fractionation of a chloroform extract from pulverized rhizomes of Valeriana wallichii with focus on isolation and structure elucidation of the antileishmanial active principles.
N2  - Die vorliegende Studie beschäftigt sich mit der bioaktivitätsgeleiteten Fraktionierung eines Chloroformextraktes aus pulverisierten Rhizomen von Valeriana wallichii mit Schwerpunkt auf der Isolierung und Strukturaufklärung des antileishmanialen Wirkprinzips.
KW  - Leishmaniose
KW  - Valeriana wallichii
KW  - Extrakt
KW  - Rhizom
KW  - Naturstoff
KW  - natural products
KW  - antileishmanial
KW  - Valeriana wallichii
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129140
ER  -