Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors
Abstract: The use of light as an external trigger to change ligand shape and as a result its bioactivity, allows the probing of pharmacologically relevant systems with spatiotemporal resolution. A hetero-stilbene lead resulting from the screening of a compound that was originally designed as kinase inhibitor served as a starting point for the design of photoswitchable sirtuin inhibitors. Because the original stilbenoid structure exerted unfavourable photochemical characteristics it was remodelled to its heteroarylic diazeno analogue. By this intramolecular azologization, the shape of the molecule was left unaltered, whereas the photoswitching ability was improved. As anticipated, the highly analogous compound showed similar activity in its thermodynamically stable stretched-out (E)-form. Irradiation of this isomer triggers isomerisation to the long-lived (Z)-configuration with a bent geometry causing a considerably shorter end‐to‐end distance. The resulting affinity shifts are intended to enable real‐time photomodulation of sirtuins in vitro
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Notes
-
Beilstein journal of organic chemistry. - 15 (2019) , 2170-2183, ISSN: 1860-5397
- Event
-
Veröffentlichung
- (where)
-
Freiburg
- (who)
-
Universität
- (when)
-
2020
- Creator
-
Grathwol, Christoph Werner
Wössner, Natalie
Swyter, Sören
Smith, Adam C.
Tapavicza, Enrico
Hofstetter, Robert K.
Bodtke, Anja
Jung, Manfred
Link, Andreas
- Contributor
-
Pharmazeutische und Medizinische Chemie, Arbeitskreis Manfred Jung
- DOI
-
10.3762/bjoc.15.214
- URN
-
urn:nbn:de:bsz:25-freidok-1540684
- Rights
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
25.03.2025, 1:45 PM CET
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Grathwol, Christoph Werner
- Wössner, Natalie
- Swyter, Sören
- Smith, Adam C.
- Tapavicza, Enrico
- Hofstetter, Robert K.
- Bodtke, Anja
- Jung, Manfred
- Link, Andreas
- Pharmazeutische und Medizinische Chemie, Arbeitskreis Manfred Jung
- Universität
Time of origin
- 2020
Other Objects (12)
Klinische Erfahrungen mit N1-n-Butylbiguanid in der Behandlung des Diabetes mellitus
Compton-Effekt am Proton im Bereich der ersten Resonanz : (Messung differentieller Wirkungsquerschnitte)
Synthese und Testung neuer Inhibitoren der Lysinspezifischen Demethylase 1
Activation of Sirtuin 2 Inhibitors Employing Photoswitchable Geometry and Aqueous Solubility
Photoswitchable Kinase Inhibitors to Reversibly Control Kinase Activity
Activation of sirtuin 2 inhibitors employing photoswitchable geometry and aqueous solubility
Synthese und biologische Aktivitätsbestimmung von Inhibitoren der Lysin-spezifischen Demethylase 1
Assay development and inhibitor optimization for the histone lysine methyltransferase KMT9
Synthesis and testing of inhibitors for jumonjiC domain-containing histone demethylases
Design, Synthese und Charakterisierung neuer Sirtuin Inhibitoren
Photoswitchable protein kinase Inhibitors for novel anti-cancer applications
Total synthesis and biological evaluation of histone deacetylase inhibitor WF-3161
Klinische Erfahrungen mit N1-n-Butylbiguanid in der Behandlung des Diabetes mellitus
Compton-Effekt am Proton im Bereich der ersten Resonanz : (Messung differentieller Wirkungsquerschnitte)
Synthese und Testung neuer Inhibitoren der Lysinspezifischen Demethylase 1
Activation of Sirtuin 2 Inhibitors Employing Photoswitchable Geometry and Aqueous Solubility
Photoswitchable Kinase Inhibitors to Reversibly Control Kinase Activity
Activation of sirtuin 2 inhibitors employing photoswitchable geometry and aqueous solubility
Synthese und biologische Aktivitätsbestimmung von Inhibitoren der Lysin-spezifischen Demethylase 1
Assay development and inhibitor optimization for the histone lysine methyltransferase KMT9
Synthesis and testing of inhibitors for jumonjiC domain-containing histone demethylases
Design, Synthese und Charakterisierung neuer Sirtuin Inhibitoren
Photoswitchable protein kinase Inhibitors for novel anti-cancer applications
Total synthesis and biological evaluation of histone deacetylase inhibitor WF-3161
Klinische Erfahrungen mit N1-n-Butylbiguanid in der Behandlung des Diabetes mellitus
Compton-Effekt am Proton im Bereich der ersten Resonanz : (Messung differentieller Wirkungsquerschnitte)
Synthese und Testung neuer Inhibitoren der Lysinspezifischen Demethylase 1
Activation of Sirtuin 2 Inhibitors Employing Photoswitchable Geometry and Aqueous Solubility
Photoswitchable Kinase Inhibitors to Reversibly Control Kinase Activity
Activation of sirtuin 2 inhibitors employing photoswitchable geometry and aqueous solubility
Synthese und biologische Aktivitätsbestimmung von Inhibitoren der Lysin-spezifischen Demethylase 1
Assay development and inhibitor optimization for the histone lysine methyltransferase KMT9
Synthesis and testing of inhibitors for jumonjiC domain-containing histone demethylases
Design, Synthese und Charakterisierung neuer Sirtuin Inhibitoren
Photoswitchable protein kinase Inhibitors for novel anti-cancer applications