Four New Carvotanacetone Derivatives from Sphaeranthus ukambensis, Inhibitors of the Ubiquitin-Proteasome Pathway
Isabelle Pouny1
, Stéphane Vispé2
, Laurence Marcourt1
, Christophe Long1
, Isabelle Vandenberghe2
, Yannick Aussagues3
, Roselyne Raux3
, Patrick B. Chalo Mutiso4
, Georges Massiot1
, François Sautel1
1Unité Mixte de Service 2597, Centre National de la Recherche Scientifique (CNRS) – Pierre Fabre, Institut des Sciences et Technologies du Médicament de Toulouse, Toulouse, France
2Centre de Recherche en Oncologie Expérimentale, Institut des Sciences et Technologies du Médicament de Toulouse (ISTMT), Toulouse, France
3Unité Mixte de Service 2646, Centre National de la Recherche Scientifique (CNRS) – Pierre Fabre, Institut des Sciences et Technologies du Médicament de Toulouse (ISTMT), Toulouse, France
4School of Biological Sciences, University of Nairobi, Nairobi, Kenya
Further Information
Publication History
received October 1, 2010
revised February 22, 2011
Six carvotanacetone derivatives (1–6), amongst which four new compounds (1–4), were isolated from the aerial parts of Sphaeranthus ukambensis Vatke & O. Hoffm. The structures of the molecules were elucidated by complementary spectroscopic methods, and their biological properties were investigated using human DLD-1 colon cancer cells engineered to stably express a 4 ubiquitin-luciferase (4 Ub-Luc) reporter protein. Five of the isolated carvotanacetone derivatives (2–6) were found to inhibit the proliferation of the colon cancer cells and interfere with the ubiquitin-proteasome pathway, with potencies in a micromolar range.
Supporting information available online at http://www.thieme-connect.de/ejournals/toc/plantamedica
2
Jakupovic J, Grenz M, Bohlmann F, Mungai G M.
Carvotacetone derivatives and eudesman-12, 6β-olides from Sphaeranthus species.
Phytochemistry.
1990;
29
1213-1217
3
Zdero C, Bohlmann F, Mungai G M.
Carvotacetone derivatives and other constituents from representatives of the Sphaeranthus group.
Phytochemistry.
1991;
30
3297-3303
9
Vandenberghe I, Créancier L, Vispé S, Annereau J P, Barret J M, Pouny I, Samson A, Aussagues Y, Massiot G, Ausseil F, Bailly C, Kruczynski A.
Physalin B, a novel inhibitor of the ubiquitin-proteasome pathway, triggers NOXA-associated apoptosis.
Biochem Pharmacol.
2008;
76
453-462
