D11, a novel glycosylated diphyllin derivative, exhibits potent anticancer activity by targeting topoisomerase II alpha
文献类型：期刊论文
| 作者 | Gui, Min1; Shi, Da-Kuo2; Huang, Min1 ; Zhao, Yu2; Sun, Qi-Ming1; Zhang, Jing1; Chen, Qin1; Feng, Jian-Ming1; Liu, Chun-Hong2; Li, Ming1
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| 刊名 | INVESTIGATIONAL NEW DRUGS
 |
| 出版日期 | 2011-10 |
| 卷号 | 29期号:5页码:800-810 |
| 关键词 | Diphyllin Glycosides Topoisomerase II inhibitor Topoisomerase II ATPase |
| ISSN号 | 0167-6997 |
| DOI | 10.1007/s10637-010-9425-3 |
| 文献子类 | Article |
| 英文摘要 | Glycosylated natural products are reliable platforms for the development of anticancer drugs, simply due to the important features added by sugar appendages to the shape and the stereoelectronic properties of natural scaffolds. Herein, we indentified D11, a novel diphyllin glycoside with acetylated D-quinovose sugar moiety, as a potent topoisomerase II alpha (Topo II alpha) inhibitior. This peculiar sugar moiety endows D11 an optimal conformation with a high binding affinity for Topo II alpha via hydrogen bonding to the entrance of ATPase pocket, thereby helping achieve more potent Topo II inhibition activity compared to the aglycon diphyllin. Further biochemical insights manifested that D11 significantly inhibited Topo II alpha ATPase-catalyzed ATP hydrolysis in an ATP-dependent, but a DNA-independent manner. All these underlie the consequent superiority of D11 in the in vitro proliferation inhibition, apoptosis induction and the in vivo remarkable antitumor potency in xenograft mouse model. Moreover, D11 treatment also displayed no obvious body weight loss and other apparent toxicities, indicative of the restricted side effects by the virtue of sugar attachment. Taken together, a defined glycosylated manipulation of diphyllin may be a promising alternative approach in the development of novel Topo II inhibitors. |
| WOS关键词 | DNA CLEAVAGE COMPLEXES ; ANTITUMOR AGENTS ; INHIBITOR ; SALVICINE ; POISON ; ENZYME |
| 资助项目 | National Basic Research Program of China[2003CB716400] ; Natural Science Foundation of China for Distinguished Young Scholars[30725046] ; Natural Science Foundation of China for Innovation Research Group[30721005] |
| WOS研究方向 | Oncology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000294223500009 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278395]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Geng, MeiYu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 2.Ocean Univ China, Sch Med & Pharm, Dept Med Chem, Qingdao 266003, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gui, Min,Shi, Da-Kuo,Huang, Min,et al. D11, a novel glycosylated diphyllin derivative, exhibits potent anticancer activity by targeting topoisomerase II alpha[J]. INVESTIGATIONAL NEW DRUGS,2011,29(5):800-810. |
| APA | Gui, Min.,Shi, Da-Kuo.,Huang, Min.,Zhao, Yu.,Sun, Qi-Ming.,...&Ding, Jian.(2011).D11, a novel glycosylated diphyllin derivative, exhibits potent anticancer activity by targeting topoisomerase II alpha.INVESTIGATIONAL NEW DRUGS,29(5),800-810. |
| MLA | Gui, Min,et al."D11, a novel glycosylated diphyllin derivative, exhibits potent anticancer activity by targeting topoisomerase II alpha".INVESTIGATIONAL NEW DRUGS 29.5(2011):800-810. |
入库方式： OAI收割
来源：上海药物研究所
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