کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1399178 | 1501153 | 2013 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: 4-Bromo-2-(piperidin-1-yl)thiazol-5-yl-phenyl methanone (12b) inhibits Na+/K+-ATPase and Ras oncogene activity in cancer cells 4-Bromo-2-(piperidin-1-yl)thiazol-5-yl-phenyl methanone (12b) inhibits Na+/K+-ATPase and Ras oncogene activity in cancer cells](/preview/png/1399178.png)
The in vitro growth inhibitory activity of 26 thiazoles (including 4-halogeno-2,5-disubtituted-1,3-thiazoles) and 5 thienothiazoles was assessed on a panel of 6 human cancer cell lines, including glioma cell lines. (4-Chloro-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12a) and (4-bromo-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12b) displayed ∼10 times greater in vitro growth inhibitory activity than perillyl alcohol (POH), which therapeutically benefits glioma patients through the inhibition of both alpha-1 Na+/K+-ATPase (NAK) and Ras oncogene activity. The in vitro cytostatic activities (as revealed by quantitative videomicroscopy) displayed by 12a and 12b were independent of the intrinsic resistance to pro-apoptotic stimuli associated with cancer cells. Compounds 12a and 12b displayed relatively similar inhibitory activities on purified guinea pig brain preparations that mainly express NAK alpha-2 and alpha-3 subunits, whereas only compound 12b was efficacious against purified guinea pig kidney preparations that mainly express the NAK alpha-1 subunit, which is also expressed in gliomas, melanomas and non-small-cell lung cancers NSCLCs.
The hit compound (12b) of the current series inhibits in vitro the growth of various cancer cell lines through the targeting of the Na+/K+-ATPase and Ras oncogene signaling.Figure optionsDownload as PowerPoint slideHighlights
► Cancers associated with dismal prognoses display intrinsic resistance to apoptosis.
► Thus to conventional chemotherapy and radiotherapy.
► 12a and 12b inhibit growth in apoptosis-resistant cancer cell lines.
► 12a and 12b revealed cytostatic, not cytotoxic, effects in cancer cells.
► 12b inhibits sodium/potassium pump and Ras oncogene activity.
Journal: European Journal of Medicinal Chemistry - Volume 63, May 2013, Pages 213–223