title: A cyclodextrin-capped histone deacetylase inhibitor.
abstract: We have synthesized a β-cyclodextrin (βCD)-capped histone deacetylase (HDAC) inhibitor 3 containing an alkyl linker and a zinc-binding hydroxamic acid motif. Biological evaluation (HDAC inhibition studies) of 3 enabled us to establish the effect of replacing an aryl cap (in SAHA (vorinostat,)) 1 by a large saccharidic scaffold "cap". HDAC inhibition was observed for 3, to a lesser extent than SAHA, and rationalized by molecular docking into the active site of HDAC8. However, compound 3 displayed no cellular activity.
authors.affiliation: Dept. of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, East Sussex, UK. j.amin@sussex.ac.uk
authors.forename: Jahangir
authors.initials: J
authors.lastname: Amin
authors.forename: Antonino
authors.initials: A
authors.lastname: Puglisi
authors.forename: James
authors.initials: J
authors.lastname: Clarke
authors.forename: John
authors.initials: J
authors.lastname: Milton
authors.forename: Minghua
authors.initials: M
authors.lastname: Wang
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Paranal
authors.forename: James E
authors.initials: JE
authors.lastname: Bradner
authors.forename: John
authors.initials: J
authors.lastname: Spencer
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D062105:Molecular Docking Simulation; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism; D000077337:Vorinostat; D015032:Zinc / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D020033:Protein Isoforms; D012097:Repressor Proteins; D047392:beta-Cyclodextrins; D000077337:Vorinostat; C409470:HDAC8 protein, human; D006655:Histone Deacetylases; D015032:Zinc; C031215:betadex