化学
单胺氧化酶
立体化学
单胺氧化酶B
对接(动物)
IC50型
单胺氧化酶A
生物化学
酶
单胺类神经递质
分子模型
体外
药理学
受体
生物
血清素
护理部
医学
作者
Chao Huang,Juan Xiong,Huida Guan,Changhong Wang,Xinsheng Lei,Jin‐Feng Hu
标识
DOI:10.1016/j.bmc.2019.03.060
摘要
(R)-5-Methylmellein (5-MM), the major ingredient in the fermented mycelia of the medicinal fungus Xylaria nigripes (called Wuling Shen in Chinese)¸ was found to be a selective inhibitor against monoamine oxidase A (MAO-A) and might play an important role in the clinical usage of this edible fungus as an anti-depressive traditional Chinese medicine (TCM). Based on the discovery and hypothesis, a variety of (R)-5-MM analogs were synthesized and evaluated in vitro against two monoamine oxidase isoforms (MAO-A and MAO-B). Most synthetic analogs showed selective inhibition of MAO-A with IC50 values ranging from 0.06 to 29 µM, and compound 13aR is the most potent analog with high selectivity (IC50, MAO-A: 0.06 µM; MAO-B: >50 µM). Interestingly, the enzyme kinetics study of 13aR indicated that this ligand seemed to bind in the MAO-A active site according to so-called “tight-binding inhibition” mode. The molecular docking study of 13aR was thereafter performed in order to rationalize the obtained biological results.
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