Facultad de Ciencias, Instituto de Química, Pontificia Universidad Católica de Valparaíso, Av. Universidad #330, Curauma, Valparaíso, Chile.
Instituto de Química y Bioquímica, Facultad de Ciencias, Universidad de Valparaíso, Av. Gran Bretaña 1111, Valparaíso, Chile.
Bioorg Chem. 2020 Aug;101:103964. doi: 10.1016/j.bioorg.2020.103964. Epub 2020 May 26.
Monoamine oxidase B inhibitory activity is closely regulated by the interaction of the small molecules with the enzyme. It is therefore desirable to use theoretical approaches to design rational methods to develop new molecules to modulate specific interactions with the protein. Here, we report such methods, and we illustrate their successful implementation by studying six synthetized 3-arylcoumarins (71-76) based on them. Monoamine oxidase B inhibition is essential to maintain the balance of dopamine, and one of its major functions is to combat dopamine degradation, a phenomenon linked to Parkinson's disease. In this work, we study small-molecule inhibitors based on the 3-arylcoumarin scaffold and their monoamine oxidase B selective inhibition. We show that 3D-QSAR models, in particular CoMFA and CoMSIA, and molecular docking approaches, enhance the probability to find new interesting inhibitors, avoiding very costly and time-consuming synthesis and biological evaluations.
单胺氧化酶 B 的抑制活性受到小分子与酶相互作用的紧密调节。因此，理想情况下可以使用理论方法来设计合理的方法来开发新的分子，以调节与蛋白质的特定相互作用。在这里，我们报告了这些方法，并通过研究基于它们的六种合成的 3-芳基香豆素（71-76）来说明其成功的实施。单胺氧化酶 B 的抑制对于维持多巴胺的平衡至关重要，其主要功能之一是对抗与帕金森病有关的多巴胺降解。在这项工作中，我们研究了基于 3-芳基香豆素支架的小分子抑制剂及其对单胺氧化酶 B 的选择性抑制。我们表明，3D-QSAR 模型，特别是 CoMFA 和 CoMSIA，以及分子对接方法，提高了发现新的有趣抑制剂的可能性，避免了非常昂贵和耗时的合成和生物学评估。
