Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang City, China.
Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang City, Hunan Province, China.
Drug Dev Res. 2021 Nov;82(7):1021-1032. doi: 10.1002/ddr.21806. Epub 2021 Feb 18.
A series of compounds bearing 3',4',5'-trimethoxy module into the core structure of evodiamine were designed and synthesized. The synthesized compounds were screened in vitro for their antitumor potential. MTT results showed that compounds 14a-14c and 14i-14j had significant effects, with compound 14h being the most prominent, with an IC value of 3.3 ± 1.5 μM, which was lower than evodiamine and 5-Fu. Subsequent experiments further confirmed that compound 14h could inhibit cell proliferation and migration, and induce G2/M phase arrest to inhibit the proliferation of HGC-27 cells, which is consistent with the results of the cytotoxicity experiment. Besides, 14h could inhibit microtubule assembly and might kill tumor cells by inhibiting VEGF and glycolysis. All experimental results indicate that compound 14h might be a potential drug candidate for the treatment of gastric cancer and was worthy of further study.
设计并合成了一系列在吴茱萸碱核心结构中引入 3'，4'，5'-三甲氧基模块的化合物。对合成的化合物进行了体外抗肿瘤活性筛选。MTT 结果表明，化合物 14a-14c 和 14i-14j 具有显著的效果，其中化合物 14h 的效果最为突出，IC 值为 3.3±1.5 μM，低于吴茱萸碱和 5-Fu。后续实验进一步证实，化合物 14h 能够抑制细胞增殖和迁移，并诱导 G2/M 期阻滞，从而抑制 HGC-27 细胞的增殖，这与细胞毒性实验的结果一致。此外，14h 能够抑制微管组装，并可能通过抑制 VEGF 和糖酵解来杀死肿瘤细胞。所有实验结果表明，化合物 14h 可能是一种治疗胃癌的潜在药物候选物，值得进一步研究。
