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Synthesis, activity evaluation, and pro-apoptotic properties of novel 1,2,4-triazol-3-amine derivatives as potent anti-lung cancer agents

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journal contribution
posted on 09.07.2019, 11:41 by Xian-yu Sun, Chun-yan Zhong, Qing-qing Qiu, Zhen-wang Li, Mei-yu Liu, Xin Wang, Cheng-hao Jin

In this study, a series of 4,5-bis(substituted phenyl)-4H-1,2,4-triazol-3-amine compounds was designed, synthesised, and evaluated to determine their potential as anti-lung cancer agents. According to the results of screening of lung cancer cell lines A549, NCI-H460, and NCI-H23 in vitro, most of the synthesised compounds have potent cytotoxic activities with IC50 values ranging from 1.02 to 48.01 µM. Particularly, compound 4,5-bis(4-chlorophenyl)-4H-1,2,4-triazol-3-amine (BCTA) was the most potent anti-cancer agent, with IC50 values of 1.09, 2.01, and 3.28 µM against A549, NCI-H460, and NCI-H23 cells, respectively, meaning many-fold stronger anti-lung cancer activity than that of the chemotherapeutic agent 5-fluorouracil. We also explored the effects of BCTA on apoptosis in lung cancer cells by flow cytometry and western blotting. Our results indicated that BCTA induced apoptosis by upregulating proteins BAX, caspase 3, and PARP. Thus, the potential application of compound BCTA as a drug should be further examined.

An outstanding compound BCTA (4,5-bis(4-chlorphenyl)-4H-1,2,4-triazol-3-amine) was found to possess more potent anticancer activity against several lung cancer cells than the reference drugs 5-FU. The effects of BCTA on apoptosis and necrosis in A549 cells were analysed by Hoechst/propidium iodide (PI) double staining and early and late apoptosis were analysed by Annexin V/PI flow cytometry. Further Western bloting results revealed that BCTA could induce cell apoptosis by down-regulting Bcl-2 protein.


The authors are grateful for the financial support from the National Natural Science Foundation of China [Grant No. 81502922], and Programme for Young Scholars with Creative Talents in HeiLongJiang BaYi Agricultural University [CXRC2016-9]. Authors also thank the funding support of Heilongjiang Bayi Agricultural University graduate students innovation project [2011150102].