Design, synthesis, antitumor evaluations and molecular modeling studies of novel 3,5-substituted indolin-2-one derivatives
文献类型：期刊论文
| 作者 | Li, Hai-hong; Zhang, Xiu-hua; Tan, Jin-zhi; Chen, Li-li ; Liu, Hong; Luo, Xiao-min; Shen, Xu; Lin, Li-ping; Chen, Kai-xian; Ding, Jian
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2007-01 |
| 卷号 | 28期号:1页码:140-152 |
| 关键词 | protein-tyrosine kinase indolin-2-one antitumor drug screening assays drug design molecular models |
| ISSN号 | 1671-4083 |
| DOI | 10.1111/j.1745-7254.2007.00473.x |
| 文献子类 | Article |
| 英文摘要 | Aim: To design and synthesize a novel class of antitumor agents, featuring the 3, 5-substituted indolin-2-one framework. Methods: Based on enzyme binding features of (Z)-SU5402, introducing a beta-pyrrole group at the 3-position of the indolin-2-one core, a series of novel 3,5-substituted indolin-2-ones were designed and synthesized. Four human carcinoma cell lines of A-431, A-549, MDA-MB-468, and Autosomal Dominant Polycystic Kidney disease were chosen for the cell proliferation assay. Results: Twenty new compounds (1a-t) with E configuration have been designed, synthesized and bioassayed. Their structural features were determined by nuclear magnetic resonance (NMR) spectra, low- and high-resolution mass spectra, and confirmed by X-ray crystallography. Although the enzyme assay showed a weak inhibition effect against the epidermal growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptor and platelet-derived growth factor receptor tyrosine kinases, the cell-based antitumor activity was promising. Compounds 1g and 1h showed higher inhibitory activity toward the A-549 and MDA-MB-468 cell lines with IC50 of 0.065-9.4 umol/L. Conclusion: This study provides a new template for further development of potent antitumor drugs. |
| WOS关键词 | TYROSINE KINASE INHIBITORS ; GROWTH-FACTOR RECEPTOR ; BREAST-CANCER ; EGF RECEPTOR ; EXPRESSION ; BINDING ; DOMAIN ; ASSAY |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:2719812 |
| WOS记录号 | WOS:000243230100019 |
| 出版者 | BLACKWELL PUBLISHING |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273361]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 成果转移转化处 新药研究国家重点实验室 药物发现与设计中心 |
| 通讯作者 | Liu, Hong |
| 作者单位 | 1.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Ctr Drug Discovery & Desig, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Div Anti Tumor Pharmacol, Shanghai 201203, Peoples R China 4.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Hai-hong,Zhang, Xiu-hua,Tan, Jin-zhi,et al. Design, synthesis, antitumor evaluations and molecular modeling studies of novel 3,5-substituted indolin-2-one derivatives[J]. ACTA PHARMACOLOGICA SINICA,2007,28(1):140-152. |
| APA | Li, Hai-hong.,Zhang, Xiu-hua.,Tan, Jin-zhi.,Chen, Li-li.,Liu, Hong.,...&Jiang, Hua-liang.(2007).Design, synthesis, antitumor evaluations and molecular modeling studies of novel 3,5-substituted indolin-2-one derivatives.ACTA PHARMACOLOGICA SINICA,28(1),140-152. |
| MLA | Li, Hai-hong,et al."Design, synthesis, antitumor evaluations and molecular modeling studies of novel 3,5-substituted indolin-2-one derivatives".ACTA PHARMACOLOGICA SINICA 28.1(2007):140-152. |
入库方式： OAI收割
来源：上海药物研究所
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