School of Biology and Food Engineering, Changshu Institute of Technology, Changshu, 215500, Jiangsu, China.
College of Animal Science and Technology, Bayi Agricultural University, Daqing, 163319, Heilongjiang, China.
ChemMedChem. 2022 Feb 4;17(3):e202100676. doi: 10.1002/cmdc.202100676. Epub 2021 Nov 26.
In this study, a series of curcumin derivatives containing 1,2,3-triazole were designed and synthesized, and their inhibitory activities against the proliferation of lung cancer cells were studied. Compound 5 k (3,4-dichlorobenzyltriazole methyl curcumin) had the best activity against A549 cells, with a half-maximal inhibitory concentration (IC ) of 2.27 μM, which was approximately 10 times higher than that of the lead curcumin and higher than that of gefitinib (IC =8.64 μM). Western blotting revealed that 5 k increased the phosphorylation levels of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Compound 5 k also promoted the expression of the inhibitor of nuclear factor-κB (IκBα) and decreased that of nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3), and β-catenin. Therefore, 5 k suppresses A549 cell proliferation by activating the mitogen-activated protein kinases and suppressing NF-κB/STAT3 signaling pathways. So, 5 k can potentially be used for treating non-small cell lung cancer.
在这项研究中，设计并合成了一系列含有 1,2,3-三氮唑的姜黄素衍生物，并研究了它们对肺癌细胞增殖的抑制活性。化合物 5k（3,4-二氯苄基三唑甲基姜黄素）对 A549 细胞的活性最好，半数最大抑制浓度（IC ）为 2.27μM，约为先导化合物姜黄素的 10 倍，高于吉非替尼（IC =8.64μM）。Western blot 揭示，5k 增加了 p38、c-Jun N 端激酶（JNK）和细胞外信号调节激酶（ERK）的磷酸化水平。化合物 5k 还促进了核因子-κB（NF-κB）抑制剂（IκBα）的表达，降低了核因子-κB（NF-κB）、信号转导和转录激活因子 3（STAT3）和β-连环蛋白的表达。因此，5k 通过激活丝裂原活化蛋白激酶和抑制 NF-κB/STAT3 信号通路来抑制 A549 细胞增殖。因此，5k 可用于治疗非小细胞肺癌。
