Synthesis and Structure-Activity Relationships of N-Methyl-5,6,7-trimethoxylindoles as Novel Antimitotic and Vascular Disrupting Agents
文献类型：期刊论文
| 作者 | Zhao, Deng-Gao1; Chen, JianJun1; Du, Ya-Rong1; Ma, Yan-Yan1; Chen, Ya-Xiong2 ; Gao, Kun1; Hu, Bu-Rong2
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2013-02-28 |
| 卷号 | 56页码:1467-1477 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm3014663 |
| 文献子类 | Article |
| 英文摘要 | Several new series of 5,6,7-trimethoxyindole derivatives were synthesized and their structure-activity relationships (SARs) were studied. Some of these compounds exhibited strong antiproliferative activities in the submicromolar range. N-Methyl-5,6,7-trimethoxylindoles 21 and 31 displayed the highest antiproliferative activities, with IC50 values ranging from 22 to 125 nM in four human cancer cell lines and activated human umbilical vein endothelial cells (HUVECs). In addition to vascular disrupting activity verified by in vitro assays, compounds 21 and 31 displayed much higher selectivity for activated HUVECs versus quiescent HUVECs than those of colchicine and combretastatinA-4. The polymerization of cancer cell tubulin was inhibited and the cell cycle was arrested in the G2/M phase after treatment with 21 and 31. It was showed that 21 disrupted tumor vasculature by use of in vivo assay. Our results suggest that these two new compounds we synthesized may become the promising leads for the development of vascular disrupting agents. |
| WOS关键词 | TUBULIN POLYMERIZATION INHIBITOR ; COMBRETASTATIN A-4 ANALOGS ; ANTITUMOR-ACTIVITY ; TUMOR VASCULATURE ; POTENT ; DRUGS ; 3-AROYLINDOLES ; ANGIOGENESIS ; DISCOVERY ; DISEASE |
| 资助项目 | CAS[Y063020BRO] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000315707300008 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.186/handle/113462/48501]  |
| 专题 | 近代物理研究所_空间辐射生物研究室 |
| 通讯作者 | Gao, Kun |
| 作者单位 | 1.Lanzhou Univ, Coll Chem & Chem Engn, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China 2.Chinese Acad Sci, Inst Modern Phys, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhao, Deng-Gao,Chen, JianJun,Du, Ya-Rong,et al. Synthesis and Structure-Activity Relationships of N-Methyl-5,6,7-trimethoxylindoles as Novel Antimitotic and Vascular Disrupting Agents[J]. JOURNAL OF MEDICINAL CHEMISTRY,2013,56:1467-1477. |
| APA | Zhao, Deng-Gao.,Chen, JianJun.,Du, Ya-Rong.,Ma, Yan-Yan.,Chen, Ya-Xiong.,...&Hu, Bu-Rong.(2013).Synthesis and Structure-Activity Relationships of N-Methyl-5,6,7-trimethoxylindoles as Novel Antimitotic and Vascular Disrupting Agents.JOURNAL OF MEDICINAL CHEMISTRY,56,1467-1477. |
| MLA | Zhao, Deng-Gao,et al."Synthesis and Structure-Activity Relationships of N-Methyl-5,6,7-trimethoxylindoles as Novel Antimitotic and Vascular Disrupting Agents".JOURNAL OF MEDICINAL CHEMISTRY 56(2013):1467-1477. |
入库方式： OAI收割
来源：近代物理研究所
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