Indole-Derived Psammaplin A Analogues as Epigenetic Modulators with Multiple Inhibitory Activities. (Articolo in rivista)

Type

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

Label

• Indole-Derived Psammaplin A Analogues as Epigenetic Modulators with Multiple Inhibitory Activities. (Articolo in rivista) (literal)

Anno

• 2012-01-01T00:00:00+01:00 (literal)

Alternative label

• Pereira R, Benedetti R, Pérez-Rodríguez S, Nebbioso A, García-Rodríguez J, Carafa V, Stuhldreier M, Conte M, Rodríguez-Barrios F, Stunnenberg HG, Gronemeyer H, Altucci L, de Lera AR. (2012)
  Indole-Derived Psammaplin A Analogues as Epigenetic Modulators with Multiple Inhibitory Activities.
  in Journal of medicinal chemistry
  (literal)

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

• Pereira R, Benedetti R, Pérez-Rodríguez S, Nebbioso A, García-Rodríguez J, Carafa V, Stuhldreier M, Conte M, Rodríguez-Barrios F, Stunnenberg HG, Gronemeyer H, Altucci L, de Lera AR. (literal)

Rivista

• Journal of medicinal chemistry (Rivista)

Note

• PubMe (literal)

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

• Departamento de Química Orgánica, Universidade de Vigo, 36310 Vigo, Spain Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, Vico L. de Crecchio 7, 80138 Napoli, Italy Institute of Genetics and Biophysics (IGB), CNR, Via P. Castellino 111, 80131 Napoli, Italy NCMLS, Department of Molecular Biology, Radboud University, 6525 GA Nijmegen, The Netherlands Department of Cancer Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS, INSERM, ULP, BP 163, 67404 Illkirch Cedex, C. U. de Strasbourg, France (literal)

Titolo

• Indole-Derived Psammaplin A Analogues as Epigenetic Modulators with Multiple Inhibitory Activities. (literal)

Abstract

• A SAR study has been carried out around a modified scaffold of the natural product psammaplin A obtained by replacing the o-bromophenol unit by an indole ring. A series of indole psammaplin A constructs were generated in a short synthetic sequence that starts with the functionalization of the C3 indole position with in situ generated nitrosoacrylate, and this is followed by protection of the ?-indole-?-oximinoesters, saponification, condensation with symmetrical diamines, and deprotection. Biochemical and cellular characterization using U937 and MCF-7 cells confirmed that many of these analogues displayed more potent actitivies than the parent natural product. Moreover, in addition to the reported HDAC and DNMT dual epigenetic inhibitory profile of the parent compound, some analogues, notably 4a (UVI5008), also inhibited the NAD(+)-dependent SIRT deacetylase enzymes. The SAR study provides structural insights into the mechanism of action of these multiple epigenetic ligands and paves the way for additional structural exploration to optimize their pharmacological profiles. Because of their multi(epi)target features and their action in ex vivo samples, the indole-based psammaplin A derivatives are attractive molecules for the modulation of epigenetic disorders. (literal)

Prodotto di

• Identificazione di regolatori del differenziamento, della motilità e dell'apoptosi delle cellule staminali (SV.P15.008.001) (Modulo)
• Institute of genetics and biophysics \"Adriano Buzzati Traverso\" (IGB) (Istituto)

Autore CNR

• Lucia Altucci (Unità di personale esterno)

Incoming links:

Prodotto

• Institute of genetics and biophysics \"Adriano Buzzati Traverso\" (IGB) (Istituto)
• Identificazione di regolatori del differenziamento, della motilità e dell'apoptosi delle cellule staminali (SV.P15.008.001) (Modulo)

Autore CNR di

• Lucia Altucci (Unità di personale esterno)

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

• Journal of medicinal chemistry (Rivista)