Quantitative Structure-Activity Relationship and Complex Network Approach to Monoamine Oxidase A and B Inhibitors
Quantitative Structure-Activity Relationship and Complex Network Approach to Monoamine Oxidase A and B Inhibitors
复制标题
DOI：
10.1021/jm800656v
复制
发表时间：
2008-11-13
影响因子：
7.3
通讯作者：
Orallo, Francisco
中科院分区：
文献类型：
--
作者：
Santana, Lourdes;Gonzalez-Diaz, Humberto;Orallo, Francisco
该研究为利用复合复杂网络和QSAR方法预测MAO-A和-B抑制剂活性提供了一个新的模型。在此基础上，制备并测定了33种香豆素衍生物，并将理论预测结果与实验活性数据进行了比较。该模型正确预测了27个化合物，大多数活性衍生物对MAO-A和MAO-B异构体的IC50值均在μ M-nM范围内。化合物14具有与clorgyline相同的MAO-A抑制活性（IC50 = 7.2 nM），并且具有最高的MAO-A特异性（比MAO-B高1000倍）。另一方面，化合物24 （IC50 = 1.2 nM）和28 （IC50 = 1.5 nM）比selegiline （IC50 = 19.6 nM）具有更高的活性，并且具有较高的MAO-B选择性，对MAO-A的抑制水平分别为100倍和1600倍。
The work provides a new model for the prediction of the MAO-A and -B inhibitor activity by the use of combined complex networks and QSAR methodologies. On the basis of the obtained model, we prepared and assayed 33 coumarin derivatives, and the theoretical prediction was compared with the experimental activity data. The model correctly predicted 27 compounds, and most of the active derivatives showed IC50 values in the mu M-nM range against both the MAO-A and MAO-B isoforms. Compound 14 shows the same MAO-A inhibitory activity (IC50 = 7.2 nM), as clorgyline used as a reference inhibitor and has the highest MAO-A specificity (1000-fold higher compared to MAO-B). On the other hand, compounds 24 (IC50 = 1.2 nM) and 28 (IC50 = 1.5 nM) show higher activity than selegiline (IC50 = 19.6 nM) and high MAO-B selectivity with 100-fold and 1600-fold inhibition levels, with respect to the MAO-A isoform.