Design, Synthesis and Biological Activity of 1,2-Benzothiazine Derivatives as Potential Anticancer Agents

doi:10.6023/cjoc201402014

Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (10): 2040-2046.DOI: 10.6023/cjoc201402014 Previous Articles Next Articles

Articles

1,2-苯并噻嗪类化合物的设计、合成及抗肿瘤活性研究

王杰^a,b, 许勤龙^c, 李家明^a,b, 张恩立^a,b, 胡敏华^a,b, 叶文峰^a,b, 黄伟军^a,b

a. 安徽中医药大学安徽省现代中药重点实验室合肥 230031;
b. 安徽省中医药科学院药物化学研究所合肥 230038;
c. 合肥医工医药有限公司合肥 230059

收稿日期:2014-02-17 修回日期:2014-04-27 发布日期:2014-06-09
通讯作者: 李家明 E-mail:lijiaming2004@sina.com
基金资助:
安徽省自然科学基金（No. 1208085MH128）、国家创新药物孵化基地（No. 2012ZX09401066）资助项目.

Design, Synthesis and Biological Activity of 1,2-Benzothiazine Derivatives as Potential Anticancer Agents

Wang Jie^a,b, Xu Qinlong^c, Li Jiaming^a,b, Zhang Enli^a,b, Hu Minhua^a,b, Ye Wenfeng^a,b, Huang Weijun^a,b

a. Anhui Key Laboratory of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230031;
b. Medicinal Chemistry Department, Anhui Academy of Chinese Medicine, Hefei 230038;
c. Hefei Industrial Pharmaceutical Institute Co., Ltd., Hefei 230059

Received:2014-02-17 Revised:2014-04-27 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.

Key words: 1,2-benzothiazine derivatives, tyrosine kinase inhibitors, antitumor

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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]. Chin. J. Org. Chem., 2014, 34(10): 2040-2046.

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1,2-苯并噻嗪类化合物的设计、合成及抗肿瘤活性研究

Design, Synthesis and Biological Activity of 1,2-Benzothiazine Derivatives as Potential Anticancer Agents

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