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



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   

  1. 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;
  • 基金资助:


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

Zhang Leia, Li Wenyunb, Liu Laia, Zheng Chengyuea, Wang Yanga, Xu Yingshua, Shi Dabina, Nie Xuqianga, Guo Jiayinga, Zhu Chunyuana, Wang Jinga   

  1. 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;
  • 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.

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