Quantitative Structure−Activity Relationship and Complex Network Approach to Monoamine Oxidase A and B Inhibitors

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• 作者：Lourdes Santana ; Humberto Gonzá ; lez-Dí ; az ; Elí ; as Quezada ; Eugenio Uriarte ; Matilde Yá ; ñ ; ez ; Dolores Viñ ; a ; Francisco Orallo
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：November 13, 2008
• 年：2008
• 卷：51
• 期：21
• 页码：6740-6751
• 全文大小：421K
• 年卷期：v.51,no.21(November 13, 2008)
• ISSN：1520-4804

文摘

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 μM−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.