Novel 3-Arylideneindolin-2-ones as Inhibitors of NAD+-Dependent Histone Deacetylases (Sirtuins)

Class III histone deacetylases (sirtuins) play pivotal roles in many cellular processes. They are linked to extended lifespan and to the pathogenesis of cancer and neuronal disorders. We present novel sirtuin inhibitors based on a 6,7-dichloro-2-oxindole scaffold with low micromolar activity. In vit...

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Veröffentlicht in:	Journal of medicinal chemistry 2010-02, Vol.53 (3), p.1383-1386
Hauptverfasser:	Huber, Kilian, Schemies, Jörg, Uciechowska, Urszula, Wagner, Julia M, Rumpf, Tobias, Lewrick, Felicitas, Süss, Regine, Sippl, Wolfgang, Jung, Manfred, Bracher, Franz
Format:	Artikel
Sprache:	eng
Schlagworte:	Acetylation Antineoplastic agents Biological and medical sciences Blotting, Western Enzyme-Linked Immunosorbent Assay General aspects Histone Deacetylase Inhibitors - chemical synthesis Histone Deacetylase Inhibitors - chemistry Histone Deacetylase Inhibitors - pharmacology Humans Indoles - chemical synthesis Indoles - chemistry Indoles - pharmacology Medical sciences Miscellaneous Molecular Structure NAD - metabolism Neuropharmacology Pharmacology. Drug treatments Sirtuins - antagonists & inhibitors Sirtuins - metabolism Structure-Activity Relationship
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Zusammenfassung:	Class III histone deacetylases (sirtuins) play pivotal roles in many cellular processes. They are linked to extended lifespan and to the pathogenesis of cancer and neuronal disorders. We present novel sirtuin inhibitors based on a 6,7-dichloro-2-oxindole scaffold with low micromolar activity. In vitro activity was rationalized by docking studies, and hyperacetylation of sirtuin targets could be demonstrated in cell culture.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm901055u