Your browser doesn't support javascript.
loading
Phosphorus containing analogues of SAHA as inhibitors of HDACs.
Pun, Michael D; Wu, Hsin-Hua; Olatunji, Feyisola P; Kesic, Britany N; Peters, John W; Berkman, Clifford E.
Afiliación
  • Pun MD; Department of Chemistry, Washington State University, Pullman, WA, USA.
  • Wu HH; Department of Chemistry, Washington State University, Pullman, WA, USA.
  • Olatunji FP; Institute of Biological Chemistry, Washington State University, Pullman, WA, USA.
  • Kesic BN; Department of Chemistry, Washington State University, Pullman, WA, USA.
  • Peters JW; Department of Chemistry, Washington State University, Pullman, WA, USA.
  • Berkman CE; Department of Chemistry, Washington State University, Pullman, WA, USA.
J Enzyme Inhib Med Chem ; 37(1): 1315-1319, 2022 Dec.
Article en En | MEDLINE | ID: mdl-35514164
Histone deacetylases (HDACs) are a family of enzymes responsible for regulating DNA transcription by modulating its binding to histone proteins. HDACs are overexpressed in several types of cancers and are recognised as drug targets. Vorinostat, or suberanilohydroxamic acid (SAHA), is an histone deacetylase (HDAC) inhibitor with a hydroxamic acid as a zinc-binding group (ZBG), and it has been FDA approved for the treatment of T-cell lymphoma. In this work, phosphorus-based SAHA analogues were synthesised to assess their zinc-binding effectiveness compared to the hydroxamic acid of SAHA. Specifically, we examined phosphate, phosphoramidate and phosphorothiolate groups as isosteres of the canonical hydroxamic acid motif of conventional HDAC inhibitors. The compounds were screened for binding to HDAC enzymes from HeLa cell lysate. The most potent derivatives were then screened against HDAC3 and HDAC8 isoforms. HDAC inhibition assays demonstrated that these phosphorus-based SAHA analogs exhibited slow binding to HDACs but with greater potency than phosphonate SAHA analogs examined previously. All compounds inhibited HDACs, the most potent having an IC50 of 50 µM.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fósforo / Histona Desacetilasas Límite: Humans Idioma: En Revista: J Enzyme Inhib Med Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fósforo / Histona Desacetilasas Límite: Humans Idioma: En Revista: J Enzyme Inhib Med Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido