School of Basic Medical Science, Zhengzhou University, Zhengzhou, 450001, China; School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China.
School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China.
Eur J Med Chem. 2019 Mar 1;165:309-322. doi: 10.1016/j.ejmech.2019.01.033. Epub 2019 Jan 18.
Structurally diverse trimethoxyphenyl-1,2,3-triazole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three cancer cell lines (PC3, MGC803 and HepG2). Among them, trimethoxyphenyl-1,2,3-triazole containing the coumarin fragement 19c displayed better antiproliferative activity results with IC50 values from 0.13 μM to 1.74 μM than anticancer drug colchicine. Compound 19c could inhibit MGC803 cell growth and colony formation, induce G2/M phase arrest by down expression of CDK1, and promote apoptosis by regulating DR5 and Bcl-2 family. Moreover, 19c strongly inhibited tubulin polymerization by interacting with the colchicine site.
设计、合成了结构多样的三苯甲基-1,2,3-三唑杂合体，并评估了它们对三种癌细胞系（PC3、MGC803 和 HepG2）的抗增殖活性。其中，含有香豆素片段的三苯甲基-1,2,3-三唑 19c 表现出更好的抗增殖活性，IC50 值为 0.13 μM 至 1.74 μM，优于抗癌药物秋水仙碱。化合物 19c 可以抑制 MGC803 细胞的生长和集落形成，通过下调 CDK1 诱导 G2/M 期阻滞，并通过调节 DR5 和 Bcl-2 家族促进细胞凋亡。此外，19c 通过与秋水仙碱结合部位相互作用强烈抑制微管聚合。
