Molecular Docking, 3D‐QSAR Studies, and In Silico ADME Prediction of p‐Aminosalicylic Acid Derivatives as Neuraminidase Inhibitors
Molecular Docking, 3D‐QSAR Studies, and In Silico ADME Prediction of p‐Aminosalicylic Acid Derivatives as Neuraminidase Inhibitors
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DOI：
10.1111/j.1747-0285.2011.01179.x
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发表时间：
2011-10
影响因子：
3
通讯作者：
Jie Zhang;Y. Shan;Xiaoyan Pan;Chen Wang;Wenfang Xu;Langchong He
中科院分区：
文献类型：
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作者：
Jie Zhang;Y. Shan;Xiaoyan Pan;Chen Wang;Wenfang Xu;Langchong He
神经氨酸酶（NA）是流感病毒的主要糖蛋白，对病毒感染至关重要。它为抗病毒药物的设计和发现提供了一个潜在的靶点。为了开发新型有效的神经氨酸酶抑制剂（NAI），利用Surflex - Dock将40种疏水对氨基水杨酸衍生物连接到NA的活性位点。采用比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）对40个分子进行了三维定量构效关系研究。CoMFA （q2 = 0.628, r2 = 0.697）和CoMSIA （q2 = 0.746, r2 = 0.816）均给出了合理的结果。这些NAI的初步药代动力学特征也在Volsurf预测的基础上进行。本研究结果将为新型强效NAI的设计提供参考。
Neuraminidase (NA) is a major glycoprotein of influenza virus which is essential for viral infection. It offers a potential target for antiviral drug design and discovery. To develop novel potent neuraminidase inhibitors (NAI), Surflex‐Dock was employed to dock 40 hydrophobic p‐aminosalicylic acid derivatives into the active site of NA. The 3D‐quantitative structure–activity relationship studies involving comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 40 molecules. Both CoMFA (q2 = 0.628, r2 = 0.697) and CoMSIA (q2 = 0.746, r2 = 0.816) gave reasonable results. A preliminary pharmacokinetic profile of these NAI was also performed on the basis of Volsurf predictions. The results obtained from this study will be useful in the design of novel potent NAI.