Chinese Journal of Organic Chemistry >
Design, Synthesis and Biological Activity of 1,2-Benzothiazine Derivatives as Potential Anticancer Agents
Received date: 2014-02-17
Revised date: 2014-04-27
Online published: 2014-06-09
Supported by
Project supported by the Anhui Provincial Natural Science Foundation (No. 1208085MH128) and the National Incubator of Innovative Drugs (No. 2012ZX09401066).
Thirteen 1,2-benzothiazine derivatives 5a~11a, 5b~10b have been designed and synthesized based on bioisosterism, and the structures of the target compounds were characterized by 1H NMR, 13C NMR, IR and mass spectra. The Anti-tumor activities of the target compounds against A549, A431, MDA-MB-468, HL60 cells in vitro were investigated by methyl thiazolyl tetrazolium (MTT) method. Most of the synthesized compounds were proved to have potent antitumor activity. Among them, compound 5b showed the most potent biological activity against A549 cell line with IC50 value of 1.57 μmol/L, compound 9a against A431, A549 and MDA-MB-468 had stronger cell growth inhibitory action than gefitinib. Molecular docking was performed to position compound 5b into epidermal growth factor receptor (EGFR) binding site in order to explore the potential target.
Wang Jie , Xu Qinlong , Li Jiaming , Zhang Enli , Hu Minhua , Ye Wenfeng , Huang Weijun . Design, Synthesis and Biological Activity of 1,2-Benzothiazine Derivatives as Potential Anticancer Agents[J]. Chinese Journal of Organic Chemistry, 2014 , 34(10) : 2040 -2046 . DOI: 10.6023/cjoc201402014
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