Identification of novel 5-hydroxy-1H-indole-3-carboxylates with anti-HBV activities based on 3D QSAR studies
文献类型：期刊论文
| 作者 | Chai, Hui-fang1; Liang, Xin-xia2; Li, Lin3; Zhao, Chun-shen2; Gong, Ping4; Liang, Zhong-jie5; Zhu, Wei-liang5 ; Jiang, Hua-liang5; Luo, Cheng5
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| 刊名 | JOURNAL OF MOLECULAR MODELING
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| 出版日期 | 2011-08 |
| 卷号 | 17期号:8页码:1831-1840 |
| 关键词 | Anti-HBV Anti-hepatitis B virus activity CoMFA CoMSIA Indole derivatives QSAR Synthesis 3D QSAR |
| ISSN号 | 1610-2940 |
| DOI | 10.1007/s00894-010-0873-7 |
| 文献子类 | Article |
| 英文摘要 | Infection with hepatitis B virus (HBV) is a major cause of liver diseases such as cirrhosis and hepatocellular carcinoma. In our previous studies, we identified indole derivatives that have anti-HBV activities. In this study, we optimize a series of 5-hydroxy-1H-indole-3-carboxylates, which exhibited potent anti-HBV activities, using three-dimensional quantitative structure-activity relationship (3D QSAR) studies with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The lowest energy conformation of compound 3, which exhibited the most potent anti-HBV activity, obtained from systematic search was used as the template for alignment. The best predictions were obtained with the CoMFA standard model (q (2) = 0.689, r (2) = 0.965, SEE = 0.082, F = 148.751) and with CoMSIA combined steric, electrostatic, hydrophobic and H-bond acceptor fields (q (2) = 0.578, r (2) = 0.973, SEE = 0.078, F = 100.342). Both models were validated by an external test set of six compounds giving satisfactory prediction. Based on the clues derived from CoMFA and CoMSIA models and their contour maps, another three compounds were designed and synthesized. Pharmacological assay demonstrated that the newly synthesized compounds possessed more potent anti-HBV activities than before (IC(50): compound 35a is 3.1 mu mol/l, compound 3 is 4.1 mu mol/l). Combining the clues derived from the 3D QSAR studies and from further validation of the 3D QSAR models, the activities of the newly synthesized indole derivatives were well accounted for. Furthermore, this showed that the CoMFA and CoMSIA models proved to have good predictive ability. |
| WOS关键词 | HEPATITIS-B-VIRUS ; IN-VITRO ; ETHYL 5-HYDROXY-1H-INDOLE-3-CARBOXYLATES ; REPLICATION ; DERIVATIVES ; INFECTION ; ENTECAVIR ; CELLS |
| 资助项目 | National Natural Science Foundation of China[30901844] ; National Natural Science Foundation of China[20972174] ; Science and Technology Foundation of Guizhou Province[[2008] ; State Key Program of Basic Research of China[2009CB918502] ; Shanghai Committee of Science and Technology[10410703900] ; Shanghai Committee of Science and Technology[0843190800] ; National ST Major Project[2009ZX09501-001] ; State Key Laboratory[SIMM1004KF-15] ; Guangdong Science and Technology Department[2010A030100006] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Chemistry ; Computer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000293137800001 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278459]  |
| 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 | Chai, Hui-fang |
| 作者单位 | 1.Guiyang Coll Tradit Chinese Med, Dept Pharm, Guiyang 550002, Peoples R China; 2.Guizhou Univ, Guizhou Prov Key Lab Fermentat Engn & Biol Pharm, Guiyang 550003, Peoples R China; 3.Shanghai Changzheng Hosp, Div Nephrol, Shanghai 200003, Peoples R China; 4.Shenyang Pharmaceut Univ, Sch Pharmaceut Engn, Shenyang 110016, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chai, Hui-fang,Liang, Xin-xia,Li, Lin,et al. Identification of novel 5-hydroxy-1H-indole-3-carboxylates with anti-HBV activities based on 3D QSAR studies[J]. JOURNAL OF MOLECULAR MODELING,2011,17(8):1831-1840. |
| APA | Chai, Hui-fang.,Liang, Xin-xia.,Li, Lin.,Zhao, Chun-shen.,Gong, Ping.,...&Luo, Cheng.(2011).Identification of novel 5-hydroxy-1H-indole-3-carboxylates with anti-HBV activities based on 3D QSAR studies.JOURNAL OF MOLECULAR MODELING,17(8),1831-1840. |
| MLA | Chai, Hui-fang,et al."Identification of novel 5-hydroxy-1H-indole-3-carboxylates with anti-HBV activities based on 3D QSAR studies".JOURNAL OF MOLECULAR MODELING 17.8(2011):1831-1840. |
入库方式： OAI收割
来源：上海药物研究所
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