Synthesis of Novel Pyrazole Derivatives Containing Isatins as Potential Apoptosis Inducer in Non-small Lung Cancer A549 Cells

doi:10.6023/cjoc201704006

Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (7): 1721-1729.DOI: 10.6023/cjoc201704006 Previous Articles Next Articles

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具有靛红结构的吡唑衍生物的合成及其诱导非小细胞肺癌A549细胞凋亡的研究

张磊^a, 李文赟^b, 刘来^a, 郑诚月^a, 王杨^a, 徐应淑^a, 史大斌^a, 聂绪强^a, 国佳莹^a, 朱春媛^a, 王京^a

a. 遵义医学院药学院遵义 563003;
b. 成都大学四川抗菌素工业研究所成都 610051

收稿日期:2017-04-06 修回日期:2017-05-05 发布日期:2017-05-17
通讯作者: 张磊, 王京 E-mail:lzhang@zmc.edu.cn;wangjing@zmc.edu.cn
基金资助:
贵州省科技厅（Nos.[2014]7565，[2014]7557，[2015]6010）、遵义医学院博士科研启动基金（No.F-631）、国家级大学生创新创业（No.201510661009）、遵义医学院大学生创新创业（Nos.[2014]5811，[2014]2918）和遵义医学院学科建设（药物化学）资助项目.

Synthesis of Novel Pyrazole Derivatives Containing Isatins as Potential Apoptosis Inducer in Non-small Lung Cancer A549 Cells

Zhang Lei^a, Li Wenyun^b, Liu Lai^a, Zheng Chengyue^a, Wang Yang^a, Xu Yingshu^a, Shi Dabin^a, Nie Xuqiang^a, Guo Jiaying^a, Zhu Chunyuan^a, Wang Jing^a

a. School of Pharmacy, Zunyi Medical University, Zunyi 563003;
b. Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610051

Received:2017-04-06 Revised:2017-05-05 Published:2017-05-17
Contact: 10.6023/cjoc201704006 E-mail:lzhang@zmc.edu.cn;wangjing@zmc.edu.cn
Supported by:
Project supported by the Department of Science and Technology of Guizhou Province (Nos.[2014]7565,[2014]7557,[2015]6010),the Priming Scientific Research Foundation for Doctoral Program of Zunyi Medical University (No.F-631),the National Undergraduate Training Programs for Innovation and Entrepreneurship (No.201510661009),the Undergraduate Training Programs for Innovation and Entrepreneurship of Zunyi Medical University (Nos.[2014]5811,[2014]2918) and the Discipline Construction Funding (Medicinal Chemistry) of Zunyi Medical University.

1. Synthesis of Novel Pyrazole Derivatives Containing Isatins as Potential Apoptosis Inducer in Non-small Lung Cancer A549 Cells.PDF(2862KB)

Abstract

Two kinds of novel pyrazole derivatives containing isatins, total of 12 target compounds, were prepared from 4-hydroxyacetophenone via addition, cyclization, substitution, hydrazinolysis and condensation, which were characterized by ¹H NMR, ¹³C NMR and HRMS. The anti-neoplastic activity of target molecules was evaluated against human non-small cell lung cancer cell line A549 using cell counting Kit-8 (CCK-8) assay. The data showed that several compounds possessed potential anticancer effect. Among them, N'-(3-imino-6-chloroindole-2-one)-1-benzyl-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide (7e) and N'-(3-imino-6-bromoindole-2-one)-1-benzyl-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide (7f) exhibited IC₅₀ values of 30.41 and 29.69 μmol/L, respectively. Flow cytometry showed that compound 7f could induce apoptosis of A549 cells, reduce the mitochondrial membrane potential, but have no effect on the cell cycle. Those data indicated that the anti-proliferative activity of molecule 7f was mediated by apoptosis-dependent mechanism involving the mitochondrial pathway in A549 cells.

Key words: pyrazole, isatin, antineoplastic activity, cell apoptosis, mitochondrial membrane potential

Cite this article

Zhang Lei, Li Wenyun, Liu Lai, Zheng Chengyue, Wang Yang, Xu Yingshu, Shi Dabin, Nie Xuqiang, Guo Jiaying, Zhu Chunyuan, Wang Jing. Synthesis of Novel Pyrazole Derivatives Containing Isatins as Potential Apoptosis Inducer in Non-small Lung Cancer A549 Cells[J]. Chin. J. Org. Chem., 2017, 37(7): 1721-1729.

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具有靛红结构的吡唑衍生物的合成及其诱导非小细胞肺癌A549细胞凋亡的研究

Synthesis of Novel Pyrazole Derivatives Containing Isatins as Potential Apoptosis Inducer in Non-small Lung Cancer A549 Cells

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