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© Yang SI, Institut Pasteur
Publication : Bioorganic & medicinal chemistry

Semisynthetic neoboutomellerone derivatives as ubiquitin-proteasome pathway inhibitors

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Bioorganic & medicinal chemistry - 08 Dec 2011

Beck J, Guminski Y, Long C, Marcourt L, Derguini F, Plisson F, Grondin A, Vandenberghe I, Vispé S, Brel V, Aussagues Y, Ausseil F, Arimondo PB, Massiot G, Sautel F, Cantagrel F

Link to Pubmed [PMID] – 22206869

Bioorg. Med. Chem. 2012 Jan;20(2):819-31

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.

https://www.ncbi.nlm.nih.gov/pubmed/22206869