Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences and Isfahan Pharmaceutical Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
J Comput Aided Mol Des. 2012 Mar;26(3):349-61. doi: 10.1007/s10822-012-9561-2. Epub 2012 Mar 28.
3-Hydroxypyridine-4-one derivatives have shown good inhibitory activity against bacterial strains. In this work we report the application of MOLMAP descriptors based on empirical physicochemical properties with genetic algorithm partial least squares (GA-PLS) and counter propagation artificial neural networks (CP-ANN) methods to propose some novel 3-hydroxypyridine-4-one derivatives with improved antibacterial activity against Staphylococcus aureus. A large collection of 302 novel derivatives of this chemical scaffold was selected for this purpose. The activity classes of these compounds were determined using the two quantitative structure activity relationships models. To evaluate the predictability and accuracy of the obtained models, nineteen compounds belonging to all three activity classes were prepared and the activity of them was determined against S. aureus. Comparing the experimental results and the predicted activity classes revealed the accuracy of the obtained models. Seventeen of the nineteen synthesized molecules were correctly predicted by GA-PLS model according to the antimicrobial evaluation method. Molecules 5f and 5h proved to be moderately active and active experimentally, but were predicted as inactive and moderately active compounds, respectively by this model. The CP-ANN based prediction was correct for sixteen out of the nineteen synthesized molecules. 5a, 5h and 5q were moderately active and active based on the antimicrobial assays, but they were introduced as members of inactive, moderately active and inactive classes of compounds, respectively according to CP-ANN model.
3-羟基吡啶-4-酮衍生物对细菌表现出良好的抑制活性。在这项工作中，我们报告了基于经验物理化学性质的 MOLMAP 描述符与遗传算法偏最小二乘（GA-PLS）和对传播人工神经网络（CP-ANN）方法的应用，以提出一些新的具有改善的抗金黄色葡萄球菌活性的 3-羟基吡啶-4-酮衍生物。为此目的选择了 302 种这种化学支架的新型衍生物的大量集合。使用两种定量构效关系模型确定这些化合物的活性类别。为了评估获得模型的可预测性和准确性，制备了属于所有三个活性类别的十九种化合物，并测定了它们对金黄色葡萄球菌的活性。比较实验结果和预测的活性类别表明了获得模型的准确性。根据抗菌评估方法，GA-PLS 模型正确预测了十九种合成分子中的十七种。分子 5f 和 5h 在实验中被证明具有中等活性和活性，但根据该模型被预测为非活性和中等活性化合物。基于 CP-ANN 的预测对于十九种合成分子中的十六种是正确的。5a、5h 和 5q 根据抗菌测定具有中等活性和活性，但根据 CP-ANN 模型，它们分别被引入非活性、中等活性和非活性化合物类别。
