Discovery, synthesis, biological evaluation and molecular docking study of (R)-5-methylmellein and its analogs as selective monoamine oxidase A inhibi...

Basic Information

ID: ALA4392854

Journal: Bioorg Med Chem

Title: Discovery, synthesis, biological evaluation and molecular docking study of (R)-5-methylmellein and its analogs as selective monoamine oxidase A inhibitors.

Authors: Huang C, Xiong J, Guan HD, Wang CH, Lei X, Hu JF.

Abstract: (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.

CiteXplore: 30975503

DOI: 10.1016/j.bmc.2019.03.060

Patent ID: ┄