Design and synthesis of guaianolide-germacranolide heterodimers as novel anticancer agents against hepatocellular carcinoma
文献类型：期刊论文
| 作者 | Yan,Jia-Xin; Li,Qi-Hao; Li,Tian-Ze; Huang,Zhi-Yan; Ma,Yun-Bao; Chen,Ji-Jun
|
| 刊名 | DRUG DEVELOPMENT RESEARCH
 |
| 出版日期 | 2023 |
| 关键词 | antihepatoma effects guaianolide-germacranolide heterodimers PDGFRA DERIVATIVES |
| ISSN号 | 1098-2299 |
| DOI | 10.1002/ddr.22087 |
| 英文摘要 | Inspired by our previous finding that disesquiterpenoids showed more potent antihepatoma cytotoxicity than their corresponding parent monomers, natural product-like guaianolide-germacranolide heterodimers were designed and synthesized from guaianolide diene and germacranolides via a biomimetic Diels-Alder reaction to provide three antihepatoma active dimers with novel scaffolds. To explore the structure-activity relationship, 31 derivatives containing ester, carbamate, ether, urea, amide, and triazole functional groups at C-14 & PRIME; were synthesized and evaluated for their cytotoxic activities against HepG2, Huh7, and SK-Hep-1 cell lines. Among them, 25 compounds were more potent than sorafenib against HepG2 cells, 15 compounds were stronger than sorafenib against Huh7 cells, and 17 compounds were stronger than sorafenib against SK-Hep-1 cells. Compound 23 showed the most potent cytotoxicity against three hepatoma cell lines with IC50 values of 4.4 & mu;M (HepG2), 3.7 & mu;M (Huh7), and 3.1 & mu;M (SK-Hep-1), which were 2.7-, 2.2-, and 2.8-fold more potent than sorafenib, respectively. The underlying mechanism study demonstrated that compound 23 could induce cell apoptosis, prevent cell migration and invasion, cause G2/M phase arrest in SK-Hep-1 cells. Network pharmacology analyses predicted PDGFRA was one of the potential targets of compound 23, and surface plasmon resonance (SPR) assay verified that 23 had strong affinity with PDGFRA with a dissociatin constant (KD) value of 90.2 nM. These promising findings revealed that structurally novel guaianolide-germacranolide heterodimers might provide a new inspiration for the discovery of antihepatoma agents. |
| 学科主题 | Pharmacology & Pharmacy |
| WOS记录号 | WOS:001013790700001 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/75318]  |
| 专题 | 中国科学院昆明植物研究所 |
| 推荐引用方式 GB/T 7714 | Yan,Jia-Xin,Li,Qi-Hao,Li,Tian-Ze,et al. Design and synthesis of guaianolide-germacranolide heterodimers as novel anticancer agents against hepatocellular carcinoma[J]. DRUG DEVELOPMENT RESEARCH,2023. |
| APA | Yan,Jia-Xin,Li,Qi-Hao,Li,Tian-Ze,Huang,Zhi-Yan,Ma,Yun-Bao,&Chen,Ji-Jun.(2023).Design and synthesis of guaianolide-germacranolide heterodimers as novel anticancer agents against hepatocellular carcinoma.DRUG DEVELOPMENT RESEARCH. |
| MLA | Yan,Jia-Xin,et al."Design and synthesis of guaianolide-germacranolide heterodimers as novel anticancer agents against hepatocellular carcinoma".DRUG DEVELOPMENT RESEARCH (2023). |
入库方式： OAI收割
来源：昆明植物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。