Synthesis and Biological Evaluation of 2,4,5-Substituted Pyrimidines as a New Class of Tubulin Polymerization Inhibitors
文献类型：期刊论文
| 作者 | Xie, Fuchun; Zhao, Hongbing; Li, Dewen; Chen, Hong; Quan, Haitian ; Shi, Xiaojing; Lou, Liguang; Hu, Youhong
|
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2011-05-12 |
| 卷号 | 54期号:9页码:3200-3205 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm101388d |
| 文献子类 | Article |
| 英文摘要 | Members of a series of 2,4,5-substituted pyrimidine derivatives were synthesized, and their interactions with tubulin and their antiproliferative activities against the human hepatocellular carcinoma cells of liver (BEL-7402) were evaluated. One member of this family, the indole-pyrimidine 4k, having an indole-aryl-substituted aminopyrimidine structure, was observed to be an excellent inhibitor of tubulin polymerization (IC(50) = 0.79 mu M) and to display significantly high antiproliferative activities against several cancer cell lines with IC(50) values ranging from 16 to 62 nM. This substance displayed a high propensity to arrests cells at the G(2)/M phase of the cell cycle (EC(50) = 20 nM). In addition, 4k was found to competitively inhibit colchicine binding to tubulin, indicating that it binds to the colchicine-binding site of tubulin. The observations made in this investigation demonstrate that 2,4,5-substituted pyrimidines represent a new class of tubulin polymerization inhibitors with significant antiproliferative activity. |
| WOS关键词 | ANTICANCER AGENTS ; BINDING-SITE ; NATURAL-PRODUCTS ; SOLID TUMORS ; POTENT ; DERIVATIVES ; IDENTIFICATION ; ABSENCE ; CELLS |
| 资助项目 | National Science and Technology "Creation of major new drugs"[2009ZX09301-001] ; Shanghai Commission of Science and Technology[10431902900] ; National Natural Science Foundation of China[30873142] ; National Natural Science Foundation of China[90813009] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000290126800006 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278530]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物化学研究室 |
| 通讯作者 | Lou, Liguang |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xie, Fuchun,Zhao, Hongbing,Li, Dewen,et al. Synthesis and Biological Evaluation of 2,4,5-Substituted Pyrimidines as a New Class of Tubulin Polymerization Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2011,54(9):3200-3205. |
| APA | Xie, Fuchun.,Zhao, Hongbing.,Li, Dewen.,Chen, Hong.,Quan, Haitian.,...&Hu, Youhong.(2011).Synthesis and Biological Evaluation of 2,4,5-Substituted Pyrimidines as a New Class of Tubulin Polymerization Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,54(9),3200-3205. |
| MLA | Xie, Fuchun,et al."Synthesis and Biological Evaluation of 2,4,5-Substituted Pyrimidines as a New Class of Tubulin Polymerization Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 54.9(2011):3200-3205. |
入库方式： OAI收割
来源：上海药物研究所
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