Carbamates as potential prodrugs and a new<br>warhead for HDAC inhibition
Abstract: We designed and synthesized carbamates of the clinically-approved HDAC (histone deacetylase) inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) in order to validate our previously-proposed hypothesis that these carbamates might serve as prodrugs for hydroxamic acid containing HDAC inhibitors. Biochemical assays proved our new compounds to be potent inhibitors of histone deacetylases in vitro, and they also showed antiproliferative effects in leukemic cells. These results, as well as stability analysis led to the suggestion that the intact carbamates are inhibitors of histone deacetylases themselves, representing a new zinc-binding warhead in HDAC inhibitor design. This suggestion was further supported by the synthesis and evaluation of a carbamate derivative of the HDAC6-selective inhibitor bufexamac
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Molecules. 23, 2 (2018), article no. 321, DOI 10.3390/molecules23020321, issn: 1420-3049
- Keyword
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Epigenetik
Sirtuine
Histon-Deacetylase
Hydroxamsäuren
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2018
- Creator
- Contributor
- DOI
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10.3390/molecules23020321
- URN
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urn:nbn:de:bsz:25-freidok-151361
- Rights
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Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:59 AM CEST
Data provider
This object is provided by:
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Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- King, Kristina
- Hauser, Alexander-Thomas
- Melesina, Jelena
- Sippl, Wolfgang
- Jung, Manfred
- Albert-Ludwigs-Universität Freiburg. Institut für Pharmazeutische Wissenschaften
- Albert-Ludwigs-Universität Freiburg
- Universität
Time of origin
- 2018
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