| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1393026 | European Journal of Medicinal Chemistry | 2011 | 13 Pages |
We designed the 6-fluoro-2-(3-fluorophenyl)-4-substituted anilinoquinazoline derivatives as less toxic anti-cancer candidates. Our result demonstrated that LJJ-10 has greater cytotoxicity than that of the other compounds in human osteogenic sarcoma U-2 OS cells. LJJ-10-induced apoptosis was associated with enhancing ROS generation, DNA damage, and an increase of the protein levels of Fas, FasL, FADD, caspase-8, cytochrome c, Apaf-1, AIF, Endo G, caspase-9 and caspase-3 in U-2 OS cells. LJJ-10-triggered growth inhibition was significantly attenuated by N-acetylcysteine, cyclosporine A, anti-FasL monoclonal antibody, and caspase-8, -9 and -3 specific inhibitors in U-2 OS cells. We suggest that LJJ-10-induced apoptotic cell death in U-2 OS cells through death receptor- and mitochondria-dependent apoptotic signaling pathways.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We designed the 6-fluoro-(3-fluorophenyl)-4-(3-methoxyanilino)quinazoline (compound 13, LJJ-10) and fount that it has greater cytotoxicity than that of the other compounds in human osteogenic sarcoma U-2 OS cells. ► In this study, we investigated anti-cancer activity and apoptotic mechanisms of the LJJ-10 in U-2 OS cells in vitro. ► Based on these observations, we suggest that LJJ-10-induced cell death in U-2 OS cells through death receptor- and mitochondria-dependent apoptotic signaling pathways.
