Quantum Chemistry Calculation-Aided Structural Optimization of Combretastatin A-4-like Tubulin Polymerization Inhibitors: Improved Stability and Biological Activity
文献类型：期刊论文
| 作者 | Jiang, Junhang1; Zheng, Canhui1; Zhu, Kongkai2; Liu, Jia1 ; Sun, Nannan1; Wang, Chongqing1; Jiang, Hualiang2,3; Zhu, Ju1; Luo, Cheng2; Zhou, Youjun1
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2015-03-12 |
| 卷号 | 58期号:5页码:2538-2546 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.5b00118 |
| 文献子类 | Article |
| 英文摘要 | A potent combretastatin A-4 (CA-4) like tubulin polymerization inhibitor 22b was found with strong antitumor activity previously. However, it easily undergoes cis-trans isomerization under natural light, and the resulting decrease in activity limits its further applications. In this study, we used quantum chemistry calculations to explore the molecular basis of its instability. Aided by the calculations, two rounds of structural optimization of 22b were conducted. Accelerated quantitative light stability testing confirmed that the stability of these designed compounds was significantly improved as predicted. Among them, compounds 1 and 3b displayed more potent inhibitory activity on tumor cell growth than 22b. In addition, the potent in vivo antitumor activity of compound 1 was confirmed. Quantum chemistry calculations were used in the optimization of stilbene-like molecules, providing new insight into stilbenoid optimization and important implications for the future development of novel CA-4-like tubulin polymerization inhibitors. |
| WOS关键词 | POTENTIAL ANTICANCER AGENTS ; STILBENE ; ANALOGS ; PHOTOISOMERIZATION ; A-4 ; DERIVATIVES ; MECHANISM ; DESIGN ; ENERGY ; LEAD |
| 资助项目 | National Natural Science Foundation of China[21172260] ; National Natural Science Foundation of China[30901859] ; National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[81230076] ; "Chen Guang" project - Shanghai Municipal Education Commission[12CG42] ; "Chen Guang" project - Shanghai Education Development Foundation[12CG42] ; Hi-Tech Research and Development Program of China[2012AA020302] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000351186500036 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276606]  |
| 专题 | 药物发现与设计中心 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 | Zheng, Canhui |
| 作者单位 | 1.Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Junhang,Zheng, Canhui,Zhu, Kongkai,et al. Quantum Chemistry Calculation-Aided Structural Optimization of Combretastatin A-4-like Tubulin Polymerization Inhibitors: Improved Stability and Biological Activity[J]. JOURNAL OF MEDICINAL CHEMISTRY,2015,58(5):2538-2546. |
| APA | Jiang, Junhang.,Zheng, Canhui.,Zhu, Kongkai.,Liu, Jia.,Sun, Nannan.,...&Zhou, Youjun.(2015).Quantum Chemistry Calculation-Aided Structural Optimization of Combretastatin A-4-like Tubulin Polymerization Inhibitors: Improved Stability and Biological Activity.JOURNAL OF MEDICINAL CHEMISTRY,58(5),2538-2546. |
| MLA | Jiang, Junhang,et al."Quantum Chemistry Calculation-Aided Structural Optimization of Combretastatin A-4-like Tubulin Polymerization Inhibitors: Improved Stability and Biological Activity".JOURNAL OF MEDICINAL CHEMISTRY 58.5(2015):2538-2546. |
入库方式： OAI收割
来源：上海药物研究所
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