title: Molecular insights into azumamide e histone deacetylases inhibitory activity.
abstract: Azumamide E, a cyclotetrapeptide isolated from the sponge Mycale izuensis, is the most powerful carboxylic acid containing natural histone deacetylase (HDAC) inhibitor known to date. In this paper, we describe design and synthesis of two stereochemical variants of the natural product. These compounds have allowed us to clarify the influence of side chain topology on the HDAC-inhibitory activity. The present contribution also reveals the identity of the recognition pattern between azumamides and the histone deacetylase-like protein (HDLP) model receptor and reports the azumamide E unprecedented isoform selectivity on histone deacetylases class subtypes. From the present studies, a plausible model for the interaction of azumamides with the receptor binding pocket is derived, providing a framework for the rational design of new cyclotetrapeptide-based HDAC inhibitors as antitumor agents.
authors.affiliation: Department of Chemistry, University of Salerno, Via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy.
authors.forename: Nakia
authors.initials: N
authors.lastname: Maulucci
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Chini
authors.forename: Simone Di
authors.initials: SD
authors.lastname: Micco
authors.forename: Irene
authors.initials: I
authors.lastname: Izzo
authors.forename: Emiddio
authors.initials: E
authors.lastname: Cafaro
authors.forename: Adele
authors.initials: A
authors.lastname: Russo
authors.forename: Paola
authors.initials: P
authors.lastname: Gallinari
authors.forename: Chantal
authors.initials: C
authors.lastname: Paolini
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Nardi
authors.forename: Agostino
authors.initials: A
authors.lastname: Casapullo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Riccio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
authors.forename: Francesco De
authors.initials: FD
authors.lastname: Riccardis
mesh_terms: D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011161:Porifera; D011485:Protein Binding; D020033:Protein Isoforms
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; D020033:Protein Isoforms; C516229:azumanide E