Citation: 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]. Chinese Journal of Organic Chemistry, ;2017, 37(7): 1721-1729. doi: 10.6023/cjoc201704006 shu

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

Corresponding author: Zhang Lei, lzhang@zmc.edu.cn Wang Jing, wangjing@zmc.edu.cn
Received Date: 6 April 2017
Revised Date: 5 May 2017
Available Online: 17 July 2017
Fund Project: 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 Universitythe Undergraduate Training Programs for Innovation and Entrepreneurship of Zunyi Medical University [2014]5811the Priming Scientific Research Foundation for Doctoral Program of Zunyi Medical University F-631the Department of Science and Technology of Guizhou Province [2015]6010the Undergraduate Training Programs for Innovation and Entrepreneurship of Zunyi Medical University [2014]2918the National Undergraduate Training Programs for Innovation and Entrepreneurship 201510661009the Department of Science and Technology of Guizhou Province [2014]7565the Department of Science and Technology of Guizhou Province [2014]7557

Figures(9)

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.
- pyrazole,
- isatin,
- antineoplastic activity,
- cell apoptosis,
- mitochondrial membrane potential
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