Essential structural profile of a dual functional inhibitor against cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): Molecular docking and 3D-QSAR analyses on DHDMBF analogues
文献类型：期刊论文
| 作者 | Zheng, MY ; Zhang, ZS; Zhu, WL; Liu, H; Luo, XM; Chen, KX; Jiang, HL
|
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2006-05-15 |
| 卷号 | 14期号:10页码:3428-3437 |
| 关键词 | COX-2 5-LOX dual inhibitors NSAIDs DHDMBF homology modeling docking 3D-QSAR CoMFA CoMSIA |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2005.12.062 |
| 文献子类 | Article |
| 英文摘要 | It is recently proposed that compounds with equal capabilities of inhibiting COX and 5-LOX, both are key enzymes involved in the arachidonic acid (AA) cascade, are expected to be safer non-steroidal anti-inflammatory drugs (NSAIDs). To dig out helpful information in designing dual functional inhibitors against the two enzymes, homology modeling, molecular dynamics (MD) simulations, automated docking, and 3D-QSAR analyses were performed in this study on 21 COX-2/5-LOX dual inhibitors, namely, 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofuran (DHDMBF) analogues. A 3D-model of 5-LOX was built based on the high-resolution X-ray structure of rabbit reticulocyte 15-lipoxygenase. Molecular docking was then applied to locate the binding orientations and conformations of DHDMBF analogues with COX-2 and 5-LOX, respectively, leading to highly predictive CoMFA models constructed on the basis of the binding conformations with q(2) values of 0.782 and 0.634 for COX-2 and 5-LOX, respectively. In addition, CoMFA field distributions were found in good agreement with the structural characteristics of the corresponding binding sites. Both the docking simulations and QSAR analyses suggest that new potent dual inhibitors should share a structural feature with a moderately bulky group at R-2 position and a rather negatively charged group around the position of the carbonyl group of DHDMBFs. Therefore, the final 3D-QSAR models and the information of the inhibitor-enzyme interaction should be useful in developing new NSAIDs as anti-inflammation drugs with favorable safety profile. (c) 2006 Elsevier Ltd. All rights reserved. |
| WOS关键词 | ITERATIVE PARTIAL EQUALIZATION ; ORBITAL ELECTRONEGATIVITY ; 7-TERT-BUTYL-2,3-DIHYDRO-3,3-DIMETHYLBENZOFURAN DERIVATIVES ; ANALGESIC AGENTS ; ARTERIAL-WALL ; BINDING ; ATHEROSCLEROSIS ; INFLAMMATION ; PATHWAY ; 15-LIPOXYGENASE |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000236952000018 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273594]  |
| 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 | Jiang, HL |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Drug Discovery & Design Ct, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zheng, MY,Zhang, ZS,Zhu, WL,et al. Essential structural profile of a dual functional inhibitor against cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): Molecular docking and 3D-QSAR analyses on DHDMBF analogues[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2006,14(10):3428-3437. |
| APA | Zheng, MY.,Zhang, ZS.,Zhu, WL.,Liu, H.,Luo, XM.,...&Jiang, HL.(2006).Essential structural profile of a dual functional inhibitor against cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): Molecular docking and 3D-QSAR analyses on DHDMBF analogues.BIOORGANIC & MEDICINAL CHEMISTRY,14(10),3428-3437. |
| MLA | Zheng, MY,et al."Essential structural profile of a dual functional inhibitor against cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): Molecular docking and 3D-QSAR analyses on DHDMBF analogues".BIOORGANIC & MEDICINAL CHEMISTRY 14.10(2006):3428-3437. |
入库方式： OAI收割
来源：上海药物研究所
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