A New Class of Naphthalimide-Based Antitumor Agents That Inhibit Topoisomerase II and Induce Lysosomal Membrane Permeabilization and Apoptosis
文献类型：期刊论文
| 作者 | Chen, Zhuo2; Liang, Xin2; Zhang, Huanying2; Xie, Hua1,2 ; Liu, Jianwen2; Xu, Yufang2; Zhu, Weiping2; Wang, Yi1; Wang, Xin2; Tan, Shaoying2
|
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2010-03-25 |
| 卷号 | 53期号:6页码:2589-2600 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm100025u |
| 文献子类 | Article |
| 英文摘要 | Based on the advantages of multitarget drugs for cancer treatment, a new class of naphthalimides was designed, synthesized, and proved to inhibit topoisomerase II (topo II), induced lysosomal membrane permeabilization (LMP), and ultimately caused apoptosis and cell death. The majority of compounds 7a-d and 8a-d potently inhibited the growth of the five tested cancer cell lines with IC(50) values ranging from 2 to 10 mu M and are more active than amonafide, a naphthahmide that was in phase III clinical trials. These compounds were tested for their interactions with DNA and their cell-free topo II inhibition activities, which demonstrated these compounds were weak DNA binders but modest topo II inhibitors. Furthermore, compounds 7b-d were found to notably induce LMP and exhibited better antiproliferative activity compared with their single-target analogues. All of the newly synthesized compounds were demonstrated to efficiently induce apoptosis via a mitochondrial pathway. Accordingly, a new paradigm was suggested for the design of novel multitarget anticancer drugs. |
| WOS关键词 | BASIC BIOLOGICAL PHENOMENON ; DESIGNED MULTIPLE LIGANDS ; WIDE-RANGING IMPLICATIONS ; DRUG DISCOVERY PARADIGM ; TUMOR-CELL DEATH ; CANCER-THERAPY ; LYSOSOMOTROPIC DETERGENT ; ANTICANCER AGENTS ; CYTOCHROME-C ; DNA |
| 资助项目 | Key New Drug Creation and Manufacturing Program[2009ZX09103-102] ; National High Technology Research and Development Program of China[2006AA10A201] ; China 111 Project[1307023] ; Shanghai Leading Academic Discipline Project[B507] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000275711000025 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278940]  |
| 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 |
| 通讯作者 | Xu, Yufang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Chen, Zhuo,Liang, Xin,Zhang, Huanying,et al. A New Class of Naphthalimide-Based Antitumor Agents That Inhibit Topoisomerase II and Induce Lysosomal Membrane Permeabilization and Apoptosis[J]. JOURNAL OF MEDICINAL CHEMISTRY,2010,53(6):2589-2600. |
| APA | Chen, Zhuo.,Liang, Xin.,Zhang, Huanying.,Xie, Hua.,Liu, Jianwen.,...&Qian, Xuhong.(2010).A New Class of Naphthalimide-Based Antitumor Agents That Inhibit Topoisomerase II and Induce Lysosomal Membrane Permeabilization and Apoptosis.JOURNAL OF MEDICINAL CHEMISTRY,53(6),2589-2600. |
| MLA | Chen, Zhuo,et al."A New Class of Naphthalimide-Based Antitumor Agents That Inhibit Topoisomerase II and Induce Lysosomal Membrane Permeabilization and Apoptosis".JOURNAL OF MEDICINAL CHEMISTRY 53.6(2010):2589-2600. |
入库方式： OAI收割
来源：上海药物研究所
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。