title: Cross metathesis with hydroxamate and benzamide BOC-protected alkenes to access HDAC inhibitors and their biological evaluation highlighted intrinsic activity of BOC-protected dihydroxamates.
abstract: Conditions for the metathesis of alkenes in the convergent synthesis of HDAC inhibitors have been improved by continuous catalyst flow injection in the reaction media. Intermediate and target compounds obtained were tested for their ability to induce HDAC inhibition and tubulin acetylation, revealing the key role of the tert-butyloxycarbonyl (BOC) group for more HDAC6 selectivity. Molecular modelling added rationale for this BOC effect.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 Quai Ernest-Ansermet, 1211 Geneva, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Zwick
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 Quai Ernest-Ansermet, 1211 Geneva, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nurisso
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 Quai Ernest-Ansermet, 1211 Geneva, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Simões-Pires
authors.affiliation: Institut de Chimie des Milieux et Matériaux de Poitiers, UMR CNRS 7285, 4 rue Michel Brunet, TSA 521106, B28, 86073 Poitiers, France; Réseau Epigénétique du Cancéropôle Grand Ouest, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Bouchet
authors.affiliation: Institut de chimie, UMR CNRS 7272, UNSA, F-06108 Nice, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Martinet
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, 1117 Budapest Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Lehotzky
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, 1117 Budapest Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Ovadi
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 Quai Ernest-Ansermet, 1211 Geneva, Switzerland.
authors.forename: Muriel
authors.initials: M
authors.lastname: Cuendet
authors.affiliation: Inserm, UMR 892, Nantes F-44000, France; CNRS, UMR 6299, Nantes F-44000, France; University of Nantes, Nantes F-44000, France; Réseau Epigénétique du Cancéropôle Grand Ouest, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Blanquart
authors.affiliation: Institut de Chimie des Milieux et Matériaux de Poitiers, UMR CNRS 7285, 4 rue Michel Brunet, TSA 521106, B28, 86073 Poitiers, France; Réseau Epigénétique du Cancéropôle Grand Ouest, France. Electronic address: philippe.bertrand@univ-poitiers.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertrand
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D001549:Benzamides / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005563:Formic Acid Esters / Q000737:chemistry*; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000475:Alkenes; D001549:Benzamides; D005563:Formic Acid Esters; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C000345:t-butyloxycarbonyl group; C037689:benzamide; D006655:Histone Deacetylases
keywords: Cancer; Histone deacetylases; Metathesis; Tubulin