title: Azetidinones as zinc-binding groups to design selective HDAC8 inhibitors.
abstract: 2-Azetidinones, commonly known as beta-lactams, are well-known heterocyclic compounds. Herein we described the synthesis and biological evaluation of a series of novel beta-lactams. In vitro inhibition assays against HDAC isoforms showed an interesting isoform-selectivity of these compounds towards HDAC6 and HDAC8. The isoform selectivity changed in response to modification of the azetidinone-ring nitrogen atom substituent. The presence of an N-thiomethyl group is a prerequisite for the activity of these compounds in the micromolar range towards HDAC8.
authors.affiliation: Dipartimento di Chimica G. Ciamician, Università of Bologna, Via Selmi 2, 40126 Bologna, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Galletti
authors.forename: Arianna
authors.initials: A
authors.lastname: Quintavalla
authors.forename: Caterina
authors.initials: C
authors.lastname: Ventrici
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.forename: Walter
authors.initials: W
authors.lastname: Cabri
authors.forename: Sergio
authors.initials: S
authors.lastname: Penco
authors.forename: Grazia
authors.initials: G
authors.lastname: Gallo
authors.forename: Silvia
authors.initials: S
authors.lastname: Vincenti
authors.forename: Daria
authors.initials: D
authors.lastname: Giacomini
mesh_terms: D001384:Azetidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D015032:Zinc / Q000378:metabolism*
chemical_list: C116379:2-azetidinone; D001384:Azetidines; D056572:Histone Deacetylase Inhibitors; D020033:Protein Isoforms; D006655:Histone Deacetylases; D015032:Zinc