title: Novel 3-arylideneindolin-2-ones as inhibitors of NAD+ -dependent histone deacetylases (sirtuins).
abstract: 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.
authors.affiliation: Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, 81377 Munich, Germany.
authors.forename: Kilian
authors.initials: K
authors.lastname: Huber
authors.forename: Jörg
authors.initials: J
authors.lastname: Schemies
authors.forename: Urszula
authors.initials: U
authors.lastname: Uciechowska
authors.forename: Julia M
authors.initials: JM
authors.lastname: Wagner
authors.forename: Tobias
authors.initials: T
authors.lastname: Rumpf
authors.forename: Felicitas
authors.initials: F
authors.lastname: Lewrick
authors.forename: Regine
authors.initials: R
authors.lastname: Süss
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sippl
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
authors.forename: Franz
authors.initials: F
authors.lastname: Bracher
mesh_terms: D000107:Acetylation; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009243:NAD / Q000378:metabolism; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D056572:Histone Deacetylase Inhibitors; D007211:Indoles; D009243:NAD; D037761:Sirtuins