Fierro Angélica, Osorio-Olivares Mauricio, Cassels Bruce K, Edmondson Dale E, Sepúlveda-Boza Silvia, Reyes-Parada Miguel
Faculty of Chemistry and Biology, University of Santiago de Chile, Alameda, Santiago, Chile.
Bioorg Med Chem. 2007 Aug 1;15(15):5198-206. doi: 10.1016/j.bmc.2007.05.021. Epub 2007 May 22.
Four enantiomerically pure (S)-4-alkylthioamphetamine derivatives were evaluated as monoamine oxidase (MAO) inhibitors using the human and rat isoforms of the enzyme. Molecular dockings were performed in order to gain insights regarding the binding mode of these inhibitors. All compounds were potent and selective MAO-A inhibitors although different rank orders of potencies were observed against the enzymes from different species. This behavior can be rationalized on the basis of different binding modes to each enzyme, as determined in silico. These findings further support the concept that MAO inhibitory activity of novel compounds, determined with enzymes from diverse mammalian species, should be considered with caution if human MAO is the final target to be addressed.
使用该酶的人和大鼠同工型，对四种对映体纯的(S)-4-烷硫基苯丙胺衍生物作为单胺氧化酶(MAO)抑制剂进行了评估。进行了分子对接，以深入了解这些抑制剂的结合模式。所有化合物都是有效的选择性MAO-A抑制剂，尽管观察到针对不同物种酶的效价顺序不同。根据计算机模拟确定的与每种酶的不同结合模式，可以解释这种行为。这些发现进一步支持了这样一种观念，即如果人类MAO是最终要解决的目标，那么在使用来自不同哺乳动物物种的酶测定新型化合物的MAO抑制活性时应谨慎考虑。
