| N(14)-substituted evodiamine derivatives as dual topoisomerase 1/tubuli- n-Inhibiting anti-gastrointestinal tumor agents | |
| Deng, Jiedan2; Long, Lin1; Peng, Xue1; Jiang, Weifan1; Peng, Ying3; Zhang, Xi3; Zhao, Yuting5; Tian, Ying5; Wang, Zhen1,3; Zhuo, Linsheng1,4 | |
| 2023-07-05 | |
| Online publication date | 2023-04 |
| Source Publication | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY Impact Factor & Quartile |
| ISSN | 0223-5234 |
| Volume | 255 |
| page numbers | 12 |
| Abstract | Gastrointestinal tumor is an important factor threatening human health. Natural product-based drug discovery is a popular paradigm for expanding the chemical space and identifying new molecular entities that ameliorate human disease. Evodiamine-inspired medicinal chemistry presents therapeutic potential for treating tumors in different tissues via multi-target inhibition. Here, by focusing on the discovery of anti-gastrointestinal tumor drugs, a series of N(14) alkyl-substituted evodiamine derivatives were designed and synthesized. The structure-activity relationship studies culminated in the identification of the N(14)-propyl-substituted evodiamine analog 6b, which showed low nanomolar inhibitory activity against MGC-803 (IC50 = 0.09 mu M) and RKO (IC50 = 0.2 mu M) cell lines. Moreover, compound 6b was effective in inducing apoptosis, arresting the cell cycle in the G2/ M phase, and inhibiting migration and invasion of MGC-803 and RKO cell lines in a dose-dependent manner in vitro. Further antitumor mechanism studies revealed that compound 6b significantly inhibited topoisomerase 1 (inhibition rate of 58.3% at 50 mu M) and tubulin polymerization (IC50 = 5.69 mu M). Overall, compound 6b represents a promising dual topoisomerase 1/tubulin-targeting lead structure for the treatment of gastrointestinal tumor. |
| Keyword | Top 1 tubulin inhibitor Evodiamine derivatives Anti -Tumor |
| Publisher | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| DOI | 10.1016/j.ejmech.2023.115366 |
| Indexed By | SCIE ; IC |
| Language | 英语 |
| WOS Research Area | Pharmacology & Pharmacy |
| WOS Subject | Chemistry, Medicinal |
| WOS ID | WOS:000987940500001 |
| Original Document Type | Article |
| PMID | 37099835 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://ir.lzu.edu.cn/handle/262010/530637 |
| Collection | 兰州大学 |
| Corresponding Author | Wang, Zhen; Zhuo, Linsheng |
| Affiliation | 1.Univ South China, Sch Pharmaceut Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China; 2.Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China; 3.Univ South China, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China; 4.Univ South China, Hengyang Med Sch, Postdoctoral Stn Basic Med, Hengyang 421001, Hunan, Peoples R China; 5.Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China |
| Recommended Citation GB/T 7714 | Deng, Jiedan,Long, Lin,Peng, Xue,et al. N(14)-substituted evodiamine derivatives as dual topoisomerase 1/tubuli- n-Inhibiting anti-gastrointestinal tumor agents[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2023,255. |
| APA | Deng, Jiedan.,Long, Lin.,Peng, Xue.,Jiang, Weifan.,Peng, Ying.,...&Zhuo, Linsheng.(2023).N(14)-substituted evodiamine derivatives as dual topoisomerase 1/tubuli- n-Inhibiting anti-gastrointestinal tumor agents.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,255. |
| MLA | Deng, Jiedan,et al."N(14)-substituted evodiamine derivatives as dual topoisomerase 1/tubuli- n-Inhibiting anti-gastrointestinal tumor agents".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 255(2023). |
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