2. Academic Validation
  3. Semisynthetic neoboutomellerone derivatives as ubiquitin-proteasome pathway inhibitors

Semisynthetic neoboutomellerone derivatives as ubiquitin-proteasome pathway inhibitors

  • Bioorg Med Chem. 2012 Jan 15;20(2):819-31. doi: 10.1016/j.bmc.2011.11.066.
Joséphine Beck 1,  Yves Guminski,  Christophe Long,  Laurence Marcourt,  Fadila Derguini,  Fabien Plisson,  Antonio Grondin,  Isabelle Vandenberghe,  Stéphane Vispé,  Viviane Brel,  Yannick Aussagues,  Frédéric Ausseil,  Paola B Arimondo,  Georges Massiot,  François Sautel,  Frédéric Cantagrel
Affiliations

Affiliation

  • 1 USR CNRS-Pierre Fabre No. 3388 ETaC, Centre de Recherche et Développement Pierre Fabre, 3 Avenue Hubert Curien, 31035 Toulouse Cedex 01, France.
PMID: 22206869 DOI: 10.1016/j.bmc.2011.11.066
Abstract

The interesting pharmacological properties of neoboutomellerones 1 and 2 were the basis for the assembly of a small library of analogues consisting of Natural Products isolated from the plant Neoboutonia melleri and of semisynthetic derivatives. As the two enone systems (C23-C24a and C1-C3) and the two hydroxyls groups (C22 and C26) of neoboutomellerones are required for activity, modifications were focused on these functional groups. Biological evaluation by using a cellular assay for Proteasome activity provided clues regarding the mechanism of action of these Natural Products and synthetic derivatives. Certain neoboutomellerone derivatives inhibited the proliferation of human WM-266-4 melanoma tumor cells at submicromolar concentration and warrant evaluation as Anticancer agents.

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