Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma Sapienza, P.le A. Moro 5, 00185 Rome, Italy.
Eur J Med Chem. 2011 Oct;46(10):4846-52. doi: 10.1016/j.ejmech.2011.07.017. Epub 2011 Jul 19.
Several 3-carbonyl (1-26), 3-acyl (27-52), and 3-carboxyhydrazido (53-58) coumarins have been synthesized in high yields (72-99%) and tested in vitro for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity. Different substituents on the coumarin nucleus were evaluated for their effect on biological activity and isoform selectivity. Substitution at position C7 of the 3-ethyl ester coumarin ring, or the introduction of a hydrazido substituent at C3, were important to obtain highly potent and selective hMAO-B inhibitors with IC(50) values in the nanomolar range. Some derivatives were also submitted to a stability test and showed no chemical cleavage in vitro.
几种 3-羰基（1-26）、3-酰基（27-52）和 3-羧基酰肼基（53-58）香豆素已以高产率（72-99%）合成，并在体外测试其对人单胺氧化酶 A 和 B（hMAO-A 和 hMAO-B）的抑制活性。香豆素核上的不同取代基对其生物活性和同工酶选择性的影响进行了评估。3-乙酯香豆素环 C7 位的取代，或 C3 位引入酰肼取代基，对于获得高活性和选择性的 hMAO-B 抑制剂非常重要，其 IC50 值在纳摩尔范围内。一些衍生物还进行了稳定性测试，在体外没有发生化学裂解。
