Knowledge Management System of Northwest Institute of Plateau Biology, CAS
| Design, synthesis and bioactivity study of evodiamine derivatives as multifunctional agents for the treatment of hepatocellular carcinoma | |
| Fan, Xiaohong; Deng, Jiedan; Shi, Tao; Wen, Huaixiu; Li, Junfang; Liang, Ziyi; Lei, Fang; Liu, Dan; Zhang, Honghua; Liang, Yan; Hao, Xiangyong; Wang, Zhen | |
| 2021 | |
| Source Publication | BIOORGANIC CHEMISTRY
 |
| Volume | 114 |
| Abstract | Topoisomerase has been found extremely high level of expression in hepatocellular carcinoma (HCC) and proven to promote the proliferation and survival of HCC. Cancer-associated fibroblasts (CAFs) as a kind of key reactive stromal cell that abundantly present in the microenvironment of HCC, could enhance the metastatic ability and drug resistance of HCC. Therefore, developing new drugs that address the above conundrums would be of the upmost significant in the fight against HCC. Evodiamine, as a multi-target natural product, has been found to exert various biological activities such as anti-cancer and anti-hepatic fibrosis via blocking topoisomerase, NF-kappa B, TGF-beta/HGF, and Smad2/3. Inspired by these facts, 15 evodiamine derivatives were designed and synthesized for HCC treatment by simultaneously targeting Topo I and CAFs. Most of them displayed preferable anti-HCC activities on three HCC cell lines and low cytotoxicity on one normal hepatic cell. In particular, compound 8 showed the best inhibitory effect on HCC cell lines and a good inhibition on Topo I in vitro. Meanwhile, it also induced obvious G(2)/M arrest and apoptosis, and significantly decreased the migration and invasion capacity of HCC cells. In addition, compound 8 down-regulated the expression of type I collagen in the activated HSC-T6 cells, and induced the apoptosis of activated HSC-T6 cells. In vivo studies demonstrated that compound 8 markedly decreased the volume and weight of tumor (TGI = 40.53%). In vitro and in vivo studies showed that its effects were superior to those of evodiamine. This preliminary attempt may provide a promising strategy for developing anti-HCC lead compounds taking effect through simultaneous inhibition on Topo I and CAFs. |
| Keyword | Hepatocellular carcinoma Topo I Evodiamine Cancer-associated fibroblasts (CAFs) |
| Document Type | 期刊论文 |
| Identifier | http://210.75.249.4/handle/363003/60730 |
| Collection | 中国科学院西北高原生物研究所 |
| Recommended Citation GB/T 7714 | Fan, Xiaohong,Deng, Jiedan,Shi, Tao,et al. Design, synthesis and bioactivity study of evodiamine derivatives as multifunctional agents for the treatment of hepatocellular carcinoma[J]. BIOORGANIC CHEMISTRY,2021,114. |
| APA | Fan, Xiaohong.,Deng, Jiedan.,Shi, Tao.,Wen, Huaixiu.,Li, Junfang.,...&Wang, Zhen.(2021).Design, synthesis and bioactivity study of evodiamine derivatives as multifunctional agents for the treatment of hepatocellular carcinoma.BIOORGANIC CHEMISTRY,114. |
| MLA | Fan, Xiaohong,et al."Design, synthesis and bioactivity study of evodiamine derivatives as multifunctional agents for the treatment of hepatocellular carcinoma".BIOORGANIC CHEMISTRY 114(2021). |
| Files in This Item: | There are no files associated with this item. | |||||
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment