Non-Natural Macrocyclic Inhibitors of Histone Deacetylases: Design, Synthesis, and Activity (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• Non-Natural Macrocyclic Inhibitors of Histone Deacetylases: Design, Synthesis, and Activity (Articolo in rivista) (literal)

Anno

• 2010-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1021/jm101092u (literal)

Alternative label

• Auzzas L.; Larsson A.; Matera R.; Baraldi A.; Deschênes-Simard B.; Giannini G.; Cabri W.; Battistuzzi G.; Gallo G.; Ciacci A.; Vesci L.; Pisano C.; Hanessian S. (2010)
  Non-Natural Macrocyclic Inhibitors of Histone Deacetylases: Design, Synthesis, and Activity
  in Journal of medicinal chemistry
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Auzzas L.; Larsson A.; Matera R.; Baraldi A.; Deschênes-Simard B.; Giannini G.; Cabri W.; Battistuzzi G.; Gallo G.; Ciacci A.; Vesci L.; Pisano C.; Hanessian S. (literal)

Pagina inizio

• 8387 (literal)

Pagina fine

• 8399 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

• http://pubs.acs.org/doi/full/10.1021/jm101092u (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 53 (literal)

Rivista

• Journal of medicinal chemistry (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

• 23 (literal)

Note

• Scopu (literal)
• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Centre-ville, Montréal, QC, H3C 3J7 Canada; Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Traversa La Crucca 3, 07100 Sassari, Italy; Department of Chemistry, Umea University, 90187 Umea, Sweden; Sigma-Tau Research and Development, Via Pontina Km 30.400, 00040 Pomezia, Roma, Italy (literal)

Titolo

• Non-Natural Macrocyclic Inhibitors of Histone Deacetylases: Design, Synthesis, and Activity (literal)

Abstract

• Nonpeptidic chiral macrocycles were designed on the basis of an analogue of suberoylanilide hydroxamic acid (2) (SAHA, vorinostat) and evaluated against 11 histone deacetylase (HDAC) isoforms. The identification of critical amino acid residues highly conserved in the cap region of HDACs guided the design of the suberoyl-based macrocycles, which were expected to bear a maximum common substructure required to target the whole HDAC panel. A nanomolar HDAC inhibitory profile was observed for several compounds, which was comparable, if not superior, to that of 2. A promising cytotoxic activity was found for selected macrocycles against lung and colon cancer cell lines. Further elaboration of selected candidates led to compounds with an improved selectivity against HDAC6 over the other isozymes. Pair-fitting analysis was used to compare one of the best candidates with the natural tetrapeptide apicidin, in an effort to define a general pharmacophore that might be useful in the design of surrogates of peptidic macrocycles as potent and isoform-selective inhibitors. (literal)

Prodotto di

• Istituto di chimica biomolecolare (ICB) (Istituto)
• Scienze chimiche e medicinali dedicate al design di modelli innovativi di ricognizione molecolare: applicazioni per lo sviluppo di metodi e protocolli computazionali (PM.P07.008.002) (Modulo)

Autore CNR

• LUCIANA AUZZAS (Persona)

Incoming links:

Autore CNR di

• LUCIANA AUZZAS (Persona)

Prodotto

• Istituto di chimica biomolecolare (ICB) (Istituto)
• Scienze chimiche e medicinali dedicate al design di modelli innovativi di ricognizione molecolare: applicazioni per lo sviluppo di metodi e protocolli computazionali (PM.P07.008.002) (Modulo)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Journal of medicinal chemistry (Rivista)