Biological Evaluation in Vitro and in Silico of Azetidin-2-one Derivatives as Potential Anticancer Agents
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- 作者：Fabián E. Olazaran ; Gildardo Rivera ; Alondra M. Pérez-Vázquez ; Cynthia M. Morales-Reyes ; Aldo Segura-Cabrera ; Isaías Balderas-Rentería
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2017
- 出版时间：January 12, 2017
- 年：2017
- 卷：8
- 期：1
- 页码：32-37
- 全文大小：316K
- ISSN：1948-5875
文摘
Potential anticancer activity of 16 azetidin-2-one derivatives was evaluated showing that compound 6 [N-(p-methoxy-phenyl)-2-(p-methyl-phenyl)-3-phenoxy-azetidin-2-one] presented cytotoxic activity in SiHa cells and B16F10 cells. The caspase-3 assay in B16F10 cells displayed that azetidin-2-one derivatives induce apoptosis. Microarray and molecular analysis showed that compound 6 was involved on specific gene overexpression of cytoskeleton regulation and apoptosis due to the inhibition of some cell cycle genes. From the 16 derivatives, compound 6 showed the highest selectivity to neoplastic cells, it was an inducer of apoptosis, and according to an in silico analysis of chemical interactions with colchicine binding site of human α/β-tubulin, the mechanism of action could be a molecular interaction involving the amino acids outlining such binding site.