Your browser doesn't support javascript.
loading
Synthesis and Evaluation of Hybrid Structures Composed of Two Glucosylceramide Synthase Inhibitors.
van den Berg, Richard J B H N; van Rijssel, Erwin R; Ferraz, Maria Joao; Houben, Judith; Strijland, Anneke; Donker-Koopman, Wilma E; Wennekes, Tom; Bonger, Kimberly M; Ghisaidoobe, Amar B T; Hoogendoorn, Sascha; van der Marel, Gijsbert A; Codée, Jeroen D C; Overkleeft, Herman S; Aerts, Johannes M F G.
Afiliación
  • van den Berg RJ; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
  • van Rijssel ER; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
  • Ferraz MJ; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
  • Houben J; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
  • Strijland A; Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
  • Donker-Koopman WE; Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
  • Wennekes T; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
  • Bonger KM; Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB, Wageningen, The Netherlands.
  • Ghisaidoobe AB; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
  • Hoogendoorn S; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
  • van der Marel GA; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
  • Codée JD; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
  • Overkleeft HS; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
  • Aerts JM; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2300 RA, Leiden, The Netherlands. h.s.overkleeft@chem.leidenuniv.nl.
ChemMedChem ; 10(12): 2042-62, 2015 Dec.
Article en En | MEDLINE | ID: mdl-26492941
Glucosylceramide metabolism and the enzymes involved have attracted significant interest in medicinal chemistry, because aberrations in the levels of glycolipids that are derived from glucosylceramide are causative in a range of human diseases including lysosomal storage disorders, type 2 diabetes, and neurodegenerative diseases. Selective modulation of one of the glycoprocessing enzymes involved in glucosylceramide metabolism-glucosylceramide synthase (GCS), acid glucosylceramidase (GBA1), or neutral glucosylceramidase (GBA2)-is therefore an attractive research objective. In this study we took two established GCS inhibitors, one based on deoxynojirimycin and the other a ceramide analogue, and merged characteristic features to obtain hybrid compounds. The resulting 39-compound library does not contain new GCS inhibitors; however, a potent (200 nm) GBA1 inhibitor was identified that has little activity toward GBA2 and might therefore serve as a lead for further biomedical development as a selective GBA1 modulator.
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: Inhibidores Enzimáticos / Glucosiltransferasas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: ChemMedChem Asunto de la revista: FARMACOLOGIA / QUIMICA Año: 2015 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Alemania
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: Inhibidores Enzimáticos / Glucosiltransferasas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: ChemMedChem Asunto de la revista: FARMACOLOGIA / QUIMICA Año: 2015 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Alemania