期刊
MOLECULES
卷 20, 期 10, 页码 19361-19371出版社
MDPI
DOI: 10.3390/molecules201019361
关键词
sorafenib; sulfonylurea; VEGFR2; KDR kinase inhibitors; anticancer activity
资金
- National Natural Science Foundation of China [81460527]
- Natural Science Foundation of Jiangxi Province [20142BAB215020]
- Doctoral Scientific Research Foundation of Jiangxi Science & Technology Normal University
- Program of Key Laboratory of Drug Design and Optimization, Jiangxi Science & Technology Normal University [300098010306]
- College Students' Science and Technology Innovation Project of Jiangxi Province [201411318033]
Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by H-1-NMR, C-13-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3 cancer cell lines. Some of the compounds showed moderate cytotoxic activity, especially compounds 1-(2,4-difluorophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6c) and 1-(4-bromophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6f) with the IC50 values against four cancer cell lines ranging from 16.54 +/- 1.22 to 63.92 +/- 1.81 M, respectively. Inhibitory rates against vascular endothelial growth factor receptor-2 (VEGFR2/KDR) kinase at 10 M of target compounds were further carried out in this paper in order to investigate the target of these compounds. Structure-activity relationships (SARs) and docking studies indicated that the sulfonylurea unit was important to these kinds of compounds. None of the substitutions in the phenoxy group and small halogen atoms such as 2,4-difluoro substitution of the aryl group contributed to the activity. The results suggested that sulfonylurea sorafenib analogs are worthy of further study.
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