Sun, Xian-yu Zhong, Chun-yan Qiu, Qing-qing Li, Zhen-wang Liu, Mei-yu Wang, Xin Jin, Cheng-hao Synthesis, activity evaluation, and pro-apoptotic properties of novel 1,2,4-triazol-3-amine derivatives as potent anti-lung cancer agents <p>In this study, a series of 4,5-bis(substituted phenyl)-4<i>H</i>-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 <i>in vitro</i>, most of the synthesised compounds have potent cytotoxic activities with IC<sub>50</sub> values ranging from 1.02 to 48.01 µM. Particularly, compound 4,5-bis(4-chlorophenyl)-4<i>H</i>-1,2,4-triazol-3-amine (<b>BCTA</b>) was the most potent anti-cancer agent, with IC<sub>50</sub> 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 <b>BCTA</b> on apoptosis in lung cancer cells by flow cytometry and western blotting. Our results indicated that <b>BCTA</b> induced apoptosis by upregulating proteins BAX, caspase 3, and PARP. Thus, the potential application of compound <b>BCTA</b> as a drug should be further examined.</p> <p>An outstanding compound <b>BCTA</b> (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 <b>BCTA</b> 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 <b>BCTA</b> could induce cell apoptosis by down-regulting Bcl-2 protein.</p> Synthesis;anti-cancer;lung cancer;apoptosis;BCL-2 2019-07-09
    https://tandf.figshare.com/articles/journal_contribution/Synthesis_activity_evaluation_and_pro-apoptotic_properties_of_novel_1_2_4-triazol-3-amine_derivatives_as_potent_anti-lung_cancer_agents/8845295
10.6084/m9.figshare.8845295.v1