Cross metathesis with hydroxamate and benzamide BOC-protected alkenes to access HDAC inhibitors and their biological evaluation highlighted intrinsic activity of BOC-protected dihydroxamates.

Zwick, Vincent; Nurisso, Alessandra; Simões-Pires, Claudia; Bouchet, Samuel; Martinet, Nadine; Lehotzky, Attila; Ovadi, Judit; Cuendet, Muriel; Blanquart, Christophe; Bertrand, Philippe

Zwick, Vincent; Nurisso, Alessandra; Simões-Pires, Claudia; Bouchet, Samuel; Martinet, Nadine; Lehotzky, Attila; Ovadi, Judit; Cuendet, Muriel; Blanquart, Christophe; Bertrand, Philippe.

Afiliación

Zwick V; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 Quai Ernest-Ansermet, 1211 Geneva, Switzerland.
Nurisso A; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 Quai Ernest-Ansermet, 1211 Geneva, Switzerland.
Simões-Pires C; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 Quai Ernest-Ansermet, 1211 Geneva, Switzerland.
Bouchet S; 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.
Martinet N; Institut de chimie, UMR CNRS 7272, UNSA, F-06108 Nice, France.
Lehotzky A; Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, 1117 Budapest Hungary.
Ovadi J; Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, 1117 Budapest Hungary.
Cuendet M; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 Quai Ernest-Ansermet, 1211 Geneva, Switzerland.
Blanquart C; 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.
Bertrand P; 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.

Bioorg Med Chem Lett ; 26(1): 154-9, 2016 Jan 01.

Article en En | MEDLINE | ID: mdl-26611919

RESUMEN

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.

Asunto(s)

Alquenos/química; Benzamidas/química; Ésteres del Ácido Fórmico/química; Inhibidores de Histona Desacetilasas/química; Inhibidores de Histona Desacetilasas/farmacología; Histona Desacetilasas/metabolismo; Ácidos Hidroxámicos/química; Relación Dosis-Respuesta a Droga; Humanos; Modelos Moleculares; Estructura Molecular; Relación Estructura-Actividad

Palabras clave

Cancer; Histone deacetylases; Metathesis; Tubulin

Texto completo

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Benzamidas / Alquenos / Inhibidores de Histona Desacetilasas / Ésteres del Ácido Fórmico / Histona Desacetilasas / Ácidos Hidroxámicos Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2016 Tipo del documento: Article País de afiliación: Suiza

Texto completo

Imprimir

XML

PubMed Links

Buscar en Google