Chinese Journal of Organic Chemistry >
Synthesis of Novel Pyrazole Derivatives Containing Isatins as Potential Apoptosis Inducer in Non-small Lung Cancer A549 Cells
Received date: 2017-04-06
Revised date: 2017-05-05
Online published: 2017-05-17
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.
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
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