期刊
MOLECULES
卷 26, 期 21, 页码 -出版社
MDPI
DOI: 10.3390/molecules26216356
关键词
betulin derivatives; thiosemicarbazone; semicarbazone; antitumor; apoptosis
资金
- Central Government Support Fund for the Reform and Development of Local Universities-Talent Training Support Program Project [ZYZX2019]
Two new series of betulin derivatives with semicarbazone or thiosemicarbazone groups at the C-28 position were synthesized and evaluated for cytotoxicity against various cancer cell lines. Compound 8f demonstrated the most potent cytotoxicity against MCF-7 cells. Mechanism studies indicated that compound 8f may induce mitochondrial-mediated apoptosis pathway in MCF-7 cells.
Two new series of betulin derivatives with semicarbazone (7a-g) or thiosemicarbazone (8a-g) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human lung carcinoma cells (A549), human colorectal cells (HCT-116) and normal human gastric epithelial cells (GES-1). Among these compounds, 8f displayed the most potent cytotoxicity with an IC50 value of 5.86 & PLUSMN; 0.61 mu M against MCF-7 cells. Furthermore, the preliminary mechanism studies in MCF-7 cells showed that compound 8f could trigger the intracellular mitochondrial-mediated apoptosis pathway by losing MMP level, which was related with the upregulation of Bax, P53 and cytochrome c expression; the downregulation of Bcl-2 expression; activation of the expression levels of caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9; and an increase in the amounts of intracellular reactive oxygen species. These results indicated that compound 8f may be used as a valuable skeleton structure for developing novel antitumor agents.
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