400898-94-4Relevant articles and documents
Cytotoxic effects of combination of oxidosqualene cyclase inhibitors with atorvastatin in human cancer cells
Staedler, Davide,Chapuis-Bernasconi, Catherine,Dehmlow, Henrietta,Fischer, Holger,Juillerat-Jeanneret, Lucienne,Aebi, Johannes D.
supporting information; experimental part, p. 4990 - 5002 (2012/08/28)
Ten oxidosqualene cyclase inhibitors with high efficacy as cholesterol-lowering agents and of different chemical structure classes were evaluated as potential anticancer agents against human cancer cells from various tissue origins and nontumoral human-brain-derived endothelial cells. Inhibition of cancer cell growth was demonstrated at micromolar concentrations, comparable to the concentrations of statins necessary for antitumor effect. Human glioblastoma cells were among the most sensitive cells. These compounds were also able to decrease the proliferation of angiogenic brain-derived endothelial cells, as a model of tumor-induced neovasculation. Additive effects in human glioblastoma cells were also demonstrated for oxidosqualene cyclase inhibitors in combination with atorvastatin while maintaining selectivity against endothelial cells. Thus, not only statins targeting the 3-hydroxy-3- methylglutaryl coenzyme A reductase but also inhibitors of oxidosqualene cyclase decrease tumor growth, suggesting new therapeutic opportunities of combined anti-cholesterol agents for dual treatment of glioblastoma.
Oxidosqualene cyclase (OSC) inhibitors for the treatment of dyslipidemia
Dehmlow, Henrietta,Ackermann, Jean,Aebi, Johannes,Blum-Kaelin, Denise,Chucholowski, Alexander,Coassolo, Philippe,Hartman, Peter,Kansy, Manfred,Maerki, Hans Peter,Morand, Olivier,Von Der Mark, Elisabeth,Panday, Narendra,Ruf, Armin,Thoma, Ralf,Schulz-Gasch, Tanja
, p. 72 - 76 (2007/10/03)
Novel inhibitors of oxidosqualene cyclase (OSC) for the treatment of dyslipidemia are reported. Starting point for the chemistry program was a set of compounds derived from a fungicide project which, in addition to high affinity for OSC from Candida albicans, also showed high affinity for the human enzyme (hOSC). Here the evaluation process of different scaffolds is outlined for two representative series, the phenyl substituted benzo[d]isothiazoles and the aminocyclohexanes. The most promising compounds derived from the latter series were further profiled in vivo and showed promising properties with respect to modulation of lipid parameters. Schweizerische Chemische Gesellschaft.
