Triple-layered QSAR studies on substituted 1,2,4-trioxanes as potential antimalarial agents: superiority of the quantitative pharmacophore-based alignment over common substructure-based alignment.
Triple-layered QSAR studies on substituted 1,2,4-trioxanes as potential antimalarial agents: superiority of the quantitative pharmacophore-based alignment over common substructure-based alignment.
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关于取代 1,2,4-三恶烷作为潜在抗疟药物的三层 QSAR 研究：基于药效基团的定量比对优于基于常见子结构的比对。
DOI：
10.1080/1062936x.2012.742136
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发表时间：
2013
影响因子：
3
通讯作者：
Saxena,AK
中科院分区：
文献类型：
--
作者：
Gupta,AK;Saxena,AK
本研究报告了利用三种方法（药效基团、CoMFA/CoMSIA 和 HQSAR 研究）来确定 3D 化学空间中调节取代的 1,2,4-三恶烷抗疟活性的基本结构要求。 CoMFA 和 CoMSIA 研究报告了基于药效基团的定量比对 (QuantitativePBA) 相对于基于全局最小能量构象异构体的比对 (GMCBA) 的优越性。开发的模型在内部验证（q2、组交叉验证和引导）中显示出良好的统计显着性，并且在预测测试集化合物的抗疟活性方面表现良好。已发现 3D 空间中的空间、静电和疏水相互作用方面的结构特征对于取代的 1,2,4-三恶烷的抗疟活性非常重要。此外，基于相同训练和测试集的 HQSAR 研究充当了寻找替代 1,2,4-三恶烷抗疟活性亚结构指纹的附加工具。总之，这些研究可能有助于设计和发现具有有效抗疟活性的新型取代 1,2,4-三恶烷。
This study reports the utilization of three approaches – pharmacophore, CoMFA/CoMSIA and HQSAR studies – to identify the essential structural requirements in 3D chemical space for the modulation of the antimalarial activity of substituted 1,2,4-trioxanes. The superiority of quantitative pharmacophore-based alignment (QuantitativePBA) over global minima energy conformer-based alignment (GMCBA) has been reported in CoMFA and CoMSIA studies. The developed models showed good statistical significance in internal validation (q2, group cross-validation and bootstrapping) and performed very well in predicting the antimalarial activity of test set compounds. Structural features in terms of their steric, electrostatic and hydrophobic interactions in 3D space have been found to be important for the antimalarial activity of substituted 1,2,4-trioxanes. Further, the HQSAR studies based on the same training and test set acted as an additional tool to find the sub-structural fingerprints of substituted 1,2,4-trioxanes for their antimalarial activity. Together, these studies may facilitate the design and discovery of new substituted 1,2,4-trioxanes with potent antimalarial activity.