Gao En, Wang Ya, Fan Gao-Lu, Xu Guiqing, Wu Zi-Yuan, Liu Zi-Jun, Liu Jian-Cheng, Mao Long-Fei, Hou Xixi, Li Shouhu
School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453000, China.
State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.
Sci Rep. 2024 Apr 22;14(1):9223. doi: 10.1038/s41598-024-60000-1.
A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC value of 3.94 ± 0.17 µmol L (NCI-H1299), 3.16 ± 0.11 µmol L (A549), and 1.83 ± 0.13 µmol L (NCI-H1437) for 7a, and an IC value of 3.84 ± 0.22 µmol L (NCI-H1299), 3.86 ± 0.38 µmol L (A549), and 1.69 ± 0.25 µmol L (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.
设计并合成了一系列包含1,2,3-三唑部分的20种新型吉非替尼衍生物。对合成的化合物针对表皮生长因子受体（EGFR）野生型人非小细胞肺癌细胞（NCI-H1299、A549）和人肺腺癌细胞（NCI-H1437）作为非小细胞肺癌的潜在抗癌活性进行了评估。与吉非替尼相比，初步生物学评估显示，几种化合物对这些癌细胞系表现出强大的抗增殖活性。值得注意的是，化合物7a和7j表现出最显著的效果，7a在NCI-H1299中的半数抑制浓度（IC）值为3.94±0.17 μmol/L，在A549中为3.16±0.11 μmol/L，在NCI-H1437中为1.83±0.13 μmol/L；7j在NCI-H1299中的IC值为3.84±0.22 μmol/L，在A549中为3.86±0.38 μmol/L，在NCI-H1437中为1.69±0.25 μmol/L。这两种化合物可抑制H1299细胞的集落形成和迁移能力，并诱导H1299细胞凋亡。对小鼠的急性毒性实验表明化合物7a在小鼠中表现出低毒性。基于这些结果，提出7a和7j有可能被开发为治疗肺癌的新型药物。
