'Click' assembly of selective inhibitors for MAO-A.
In this Letter, an efficient strategy for the fast construction of 108 compounds library was developed using click chemistry. The fingerprint of inhibitory activity toward MAO-A/B against this library was obtained, and four hit compounds were identified as selective inhibitors toward MAO-A. Docking study was carried out to demonstrate the binding mode between a9 and MAO-A/B, and the result reveals that a9 localized in the 'aromatic cage' and oriented to establish π-π stacking interactions with Tyr407, Tyr444 and FAD in MAO-A rather than in MAO-B.
Jia
Zhao
Z
Institute of Bioengineering, Zhejiang University of Technology (chaohui campus), Hangzhou 310014, China.
Zhu
Qing
Q
D020134:Catalytic Domain; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase