3D-QSAR studies of 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids as AKR1C3 inhibitors: Highlight the importance of molecular docking in conformation generation
3D-QSAR studies of 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids as AKR1C3 inhibitors: Highlight the importance of molecular docking in conformation generation
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3-(3,4-二氢异喹啉-2(1H)-基磺酰基)苯甲酸作为 AKR1C3 抑制剂的 3D-QSAR 研究：强调分子对接在构象生成中的重要性
DOI：
10.1016/j.bmcl.2016.10.073
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发表时间：
2016
影响因子：
2.7
通讯作者：
Hai-Bin Luo
中科院分区：
文献类型：
--
作者：
Xuehua Zheng;Yinuo Wu;Deyan Wu;Xinhua Wang;Chao Zhang;Xiaolei Guo;Hai-Bin Luo
AKR 1C 3是去势抵抗性前列腺癌（CRPC）的一个有前途的药物靶点。在此，对3-（3，4-二氢异喹啉-2（1H）-基磺酰基）苯甲酸进行3D-QSAR分析，以将其化学结构与其观察到的AKR 1C 3抑制活性相关联。采用不同构象的三种结构比对方法被用来审查构象选择的QSAR模型的预测精度的影响。使用对接构象，最好的CoMFA和CoMSIA模型的开发和验证与61个分子的训练集和7个分子的测试集。等高线图的详细分析为合理设计具有增强效力的AKR 1C 3抑制剂提供了有用的结构见解。
AKR1C3 is a promising drug target for castration-resistant prostate cancer (CRPC). Here, 3D-QSAR analysis were performed on 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids to correlate their chemical structures with their observed AKR1C3 inhibitory activity. Three structural alignment methods employing various conformers were used to scrutinize the effect of conformation selection on the predictive accuracy of QSAR models. Using docked conformation, the best CoMFA and CoMSIA models were developed and validated with a training set of 61 molecules and a test set of 7 molecules. Detailed analysis of contour maps provided helpful structural insights to rational design of AKR1C3 inhibitors with enhanced potency.