Photopharmacology on Acetylcholinesterase: Novel Photoswitchable Inhibitors with Improved Pharmacological Profiles
Please always quote using this URN: urn:nbn:de:bvb:20-opus-218445
- Considerable effort has previously been invested in a light‐controlled inhibition of the enzyme acetylcholinesterase (AChE). We found that a novel azobenzene‐based bistacrine AChE inhibitor switched faster than the known dithienylethene based bistacrine and inverted the photo‐controlled interactions of the photoisomers compared to its dithienylethene congener. Furthermore, we have optimized a previously described light‐controlled tacrine‐based AChE inhibitor. Isomerization upon irradiation with UV light of the novel inhibitor was observed inConsiderable effort has previously been invested in a light‐controlled inhibition of the enzyme acetylcholinesterase (AChE). We found that a novel azobenzene‐based bistacrine AChE inhibitor switched faster than the known dithienylethene based bistacrine and inverted the photo‐controlled interactions of the photoisomers compared to its dithienylethene congener. Furthermore, we have optimized a previously described light‐controlled tacrine‐based AChE inhibitor. Isomerization upon irradiation with UV light of the novel inhibitor was observed in aqueous medium and showed no fatigue over several cycles. The cis‐enriched form showed an 8.4‐fold higher inhibition of hAChE compared with its trans‐enriched form and was about 30‐fold more active than the reference compound tacrine with a single‐digit nanomolar inhibition. We went beyond proof‐of‐concept to discover photoswitchable AChE inhibitors with pharmacologically desirable nanomolar inhibition, “cis‐on” effect, and pronounces differences between the photoisomers.…
Author: | Matthias Scheiner, Alexandra Sink, Philipp Spatz, Erik Endres, Michael Decker |
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URN: | urn:nbn:de:bvb:20-opus-218445 |
Document Type: | Journal article |
Faculties: | Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie |
Language: | English |
Parent Title (English): | ChemPhotoChem |
Year of Completion: | 2021 |
Volume: | 5 |
Issue: | 2 |
First Page: | 149 |
Last Page: | 159 |
Source: | ChemPhotoChem 2021, 5(2):149-159. DOI: 10.1002/cptc.202000119 |
DOI: | https://doi.org/10.1002/cptc.202000119 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Tag: | azobenzenes; enzymes; kinetics; photopharmacology; tacrine |
Release Date: | 2021/07/15 |
Licence (German): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |