Inhibition of monoamine oxidases by functionalized coumarin derivatives: Biological activities, QSARs, and 3D-QSARs
Inhibition of monoamine oxidases by functionalized coumarin derivatives: Biological activities, QSARs, and 3D-QSARs
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DOI：
10.1021/jm001028o
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发表时间：
2000-12-14
影响因子：
7.3
通讯作者：
Testa, B
中科院分区：
文献类型：
--
作者：
Gnerre, C;Catto, M;Testa, B
测试了大量香豆素衍生物（71种化合物）的单胺氧化酶A和B（MAO-A和MAO-B）抑制活性。大多数化合物优先作用于MAO-B，IC 50值在微摩尔至低纳摩尔范围内;还测量了磺酸酯对MAO-A的高抑制活性。最具活性的化合物是7-[（3，4-二氟苄基）氧基]-3，4-二甲基香豆素，对MAO-B的IC 50值为1.14 nM。7-X-苄氧基间位取代的3，4-二甲基香豆素衍生物作用于MAO-B的QSAR研究得到了良好的统计结果（q（2）= 0.72，r（2）= 0.86），揭示了亲脂性相互作用在调节抑制作用中的重要性，并排除了对电子性质的任何依赖性。对MAO-A和MAO-B抑制剂的两个数据集进行CoMFA。GOLPE程序，变量选择标准，应用于提高模型的预测性，并方便图形解释的结果。
A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activity. Most of the compounds acted preferentially on MAO-B with IC50 values in the micromolar to low-nanomolar range; high inhibitory activities toward MAO-A were also measured for sulfonic acid esters. The most active compound was 7-[(3,4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, with an IC50 value toward MAO-B of 1.14 nM. A QSAR study of 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin derivatives acting on MAO-B yielded good statistical results (q(2) = 0.72, r(2) = 0.86), revealing the importance of lipophilic interactions in modulating the inhibition and excluding any dependence on electronic properties. CoMFA was performed on two data sets of MAO-A and MAO-B inhibitors. The GOLPE procedure, with variable selection criteria, was applied to improve the predictivity of the models and to facilitate the graphical interpretation of results.