Falenczyk, C. and Schiedel, M. and Karaman, B. and Rumpf, T. and Kuzmanovic, N. and Grotli, M. and Sippl, W. and Jung, M. and Koenig, B. (2014) Chromo-pharmacophores: photochromic diarylmaleimide inhibitors for sirtuins. CHEMICAL SCIENCE, 5 (12). pp. 4794-4799. ISSN 2041-6520, 2041-6539
Full text not available from this repository. (Request a copy)Abstract
Controlling the activity of sirtuins is of high biomedical relevance as the enzymes are involved in cancer, neurodegeneration and other diseases. Therefore structural elements of 3,4-bisindoylmaleimides (BIMs), which are known NAD(+)-dependent histone deacetylase (sirtuin) inhibitors, were merged with photochromic diarylmaleimides to yield photoswitchable enzyme inhibitors. The new inhibitors show excellent photophysical properties, are switchable even in polar solvents, and subtype selective against hSirt2. The inhibitory activity changes up to a factor of 22 for the two photoisomers and physiological properties can therefore be effectively toggled by irradiation with light of different wavelengths. Docking experiments using the enzyme crystal structure explain the observed activity changes based on the steric demand of the thiophene substitution and the rigidity of the molecular structure.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DIARYLETHENE DERIVATIVES; DEACETYLASE; PHOTOCYCLIZATION; RECEPTORS; AGONIST; SIRT2; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Nov 2019 14:01 |
| Last Modified: | 28 Nov 2019 14:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10892 |
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