Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago 8330507, Chile.
Departamento de Química, Universidad Técnica Federico Santa María, Valparaíso 2340000, Chile.
Molecules. 2022 Jan 29;27(3):928. doi: 10.3390/molecules27030928.
Monoamine oxidases (MAOs) are attractive targets in drug design. The inhibition of one of the isoforms (A or B) is responsible for modulating the levels of different neurotransmitters in the central nervous system, as well as the production of reactive oxygen species. Molecules that act selectively on one of the MAO isoforms have been studied deeply, and coumarin has been described as a promising scaffold. In the current manuscript we describe a comparative study between 3-phenylcoumarin ( coumarin-resveratrol-inspired hybrid) and -6-styrylcoumarin ( coumarin-resveratrol-inspired hybrid). Crystallographic structures of both compounds were obtained and analyzed. 3D-QSAR models, in particular CoMFA and CoMSIA, docking simulations and molecular dynamics simulations have been performed to support and better understand the interaction of these molecules with both MAO isoforms. Both molecules proved to inhibit MAO-B, with -6-styrylcoumarin being 107 times more active than 3-phenylcoumarin, and 267 times more active than -resveratrol.
单胺氧化酶（MAO）是药物设计中的一个有吸引力的靶点。一种同工酶（A 或 B）的抑制作用负责调节中枢神经系统中不同神经递质的水平，以及活性氧的产生。对 MAO 同工酶之一具有选择性作用的分子已被深入研究，香豆素被描述为一种很有前途的支架。在当前的手稿中，我们描述了 3-苯基香豆素（香豆素-白藜芦醇灵感杂合体）和-6-苯乙烯基香豆素（香豆素-白藜芦醇灵感杂合体）之间的比较研究。获得并分析了这两种化合物的晶体结构。进行了 3D-QSAR 模型，特别是 CoMFA 和 CoMSIA，对接模拟和分子动力学模拟，以支持和更好地理解这些分子与两种 MAO 同工酶的相互作用。这两种分子都被证明抑制 MAO-B，-6-苯乙烯基香豆素比 3-苯基香豆素活性高 107 倍，比 -白藜芦醇高 267 倍。
