Key Laboratory of New Animal Drug Project, Gansu Province/Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs/Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China.
Shandong Provincial Animal and Poultry Green Health Products Creation Engineering Laboratory, Institute of Poultry Science, Shandong Academy of Agricultural Science, Jinan 250023, China.
Int J Mol Sci. 2024 Feb 13;25(4):2256. doi: 10.3390/ijms25042256.
The quantitative structure-activity relationship (QSAR) is one of the most popular methods for the virtual screening of new drug leads and optimization. Herein, we collected a dataset of 955 MIC values of pleuromutilin derivatives to construct a 2D-QSAR model with an accuracy of 80% and a 3D-QSAR model with a non-cross-validated correlation coefficient () of 0.9836 and a cross-validated correlation coefficient () of 0.7986. Based on the obtained QSAR models, we designed and synthesized pleuromutilin compounds and with thiol-functionalized side chains. Compound displayed the highest antimicrobial activity against both ATCC 29213 () and Methicillin-resistant (MRSA), with minimum inhibitory concentrations (MICs) < 0.0625 μg/mL. These experimental results confirmed that the 2D and 3D-QSAR models displayed a high accuracy of the prediction function for the discovery of lead compounds from pleuromutilin derivatives.
定量构效关系（QSAR）是新药物先导物虚拟筛选和优化的最流行方法之一。在此，我们收集了 955 个截短侧耳素衍生物 MIC 值的数据集，构建了一个 2D-QSAR 模型，其准确性为 80%，以及一个 3D-QSAR 模型，其非交叉验证相关系数（）为 0.9836，交叉验证相关系数（）为 0.7986。基于获得的 QSAR 模型，我们设计并合成了具有巯基功能化侧链的截短侧耳素化合物和。化合物对 ATCC 29213（）和耐甲氧西林金黄色葡萄球菌（MRSA）均显示出最高的抗菌活性，最小抑菌浓度（MIC）<0.0625 μg/mL。这些实验结果证实，2D 和 3D-QSAR 模型对截短侧耳素衍生物的先导化合物发现具有很高的预测功能准确性。
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