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首页> 外文期刊>International Journal of Research in Medical Sciences >3-Dimensional quantitative structure-activity relationship and molecular docking studies of tetrasubstituted pyrazole derivatives as inhibitors of cyclooxygenase-2
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3-Dimensional quantitative structure-activity relationship and molecular docking studies of tetrasubstituted pyrazole derivatives as inhibitors of cyclooxygenase-2

机译：三维定量结构 - 活性关系与四氢吡唑衍生物作为环氧氧酶-2抑制剂的四氢吡唑衍生物的分子对接研究

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Background: Design and development of new drugs is simplified and made more cost-effective because of the advances in the concepts of Quantitative Structure-Activity Relationship (QSAR) studies. A methodology of QSAR studies is one of the approaches to the rational drug design. Methods: 3-Dimensional QSAR studies were performed on a series of tetrasubstituted pyrazole derivatives by using Scigress Explorer software suite. Docking studies of these compounds were also performed to understand the interactions with amino acid residues of COX-2 protein. Results: The multiple linear regression analysis was used to correlate the physicochemical descriptors with the COX-2 inhibitory activity of 24 training set of compounds and the best QSAR model was developed. The best model was validated using leave-one-out method and found to be statistically significant, with coefficient of determination (r2) of 0.835. This model was further used to predict the COX-2 inhibitory activity of 10 test set of compounds. Docking analysis revealed that most of the compounds formed H-bond interactions with amino acid residues of COX-2 protein (PDB ID: 1CX2). Predicted pIC50 value of one of the test compounds was 7.048 and it showed H-bond interactions with His90 & Tyr355 residues. Conclusion: The present study shall help in rational drug design and synthesis of new selective COX-2 inhibitors with predetermined affinity and activity and provides valuable information for the understanding of interactions between COX-2 and the novel tetrasubstituted pyrazole derivative compounds.
机译：背景：由于定量结构 - 活动关系（QSAR）研究的概念进展，简化了新药的设计和开发更具成本效益。 QSAR研究的方法是合理药物设计的方法之一。方法：通过使用突然探索器软件套件，对一系列四取悦吡唑衍生物进行三维QSAR研究。还进行了对这些化合物的对接研究以了解与COX-2蛋白的氨基酸残基的相互作用。结果：多元线性回归分析用于将物理化学描述符与24种训练组化合物组的COX-2抑制活性相关，并且开发了最佳的QSAR模型。使用休次次方法验证了最佳模型，发现统计学意义有0.835的判定系数（R2）。该模型进一步用于预测10个测试组化合物的COX-2抑制活性。对接分析显示，大多数化合物与COX-2蛋白的氨基酸残基（PDB ID：1CX2）形成H键相互作用。预测的PIC50测试化合物的PIC50值为7.048，结果显示H键与HIS90和TYR355残基相互作用。结论：本研究应有助于具有预定亲和力和活性的合理药物设计和新选择性COX-2抑制剂的合成，并提供有价值的信息，以了解COX-2和新型四氢吡唑衍生物化合物之间的相互作用。

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