Synthesis of a series of unsaturated ketone derivatives as selective and reversible monoamine oxidase inhibitors

被引：85

作者：

Choi, Ji Won ^{[1
,2
]}

Jang, Bo Ko ^{[1
,3
]}

Cho, Nam-chul ^{[1
]}

Park, Jong-Hyun ^{[1
]}

Yeon, Seul Ki ^{[1
]}

Ju, Eun Ji ^{[1
]}

Lee, Yong Sup

Han, Gyoonhee ^{[2
]}

Pae, Ae Nim ^{[1
,4
]}

Kim, Dong Jin ^{[1
]}

Park, Ki Duk ^{[1
,4
]}

机构：

[1] Korea Inst Sci & Technol, Brain Sci Inst, Ctr Neuromed, Seoul 136791, South Korea

[2] Yonsei Univ, Dept Biotechnol, Seoul 120749, South Korea

[3] Kyung Hee Univ, Coll Pharm, Dept Pharm, Seoul 130701, South Korea

[4] Univ Sci & Technol, Dept Biol Chem, Taejon 305350, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2015年 / 23卷 / 19期

关键词：

alpha; beta-Unsaturated carbonyl derivatives; Chalcone; Monoamine oxidase; MAO-B inhibitor; Reversible inhibitor; PARKINSONS-DISEASE; CHALCONE DERIVATIVES; B INHIBITORS; AMINO-ACID; SUBSTRATE; UPDATE; MODELS; POTENT; AGENTS;

D O I：

10.1016/j.bmc.2015.08.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have synthesized three categories of alpha,beta-unsaturated carbonyl derivatives and evaluated their MAO-A and MAO-B inhibitory activities. Among them, compound 10b including alpha, beta-unsaturated ketone group showed the most potent and selective MAO-B inhibitory activity (IC50 human MAO-B 16 nM, >6000-fold selective vs MAO-A) and compound 10b exhibited good reversibility compared with selegiline, a well-known irreversible MAO-B inhibitor. However, both a, b-unsaturated amide and ester derivatives exhibited weaker MAO-B inhibition potencies. The docking studies provided insights into the possible binding modes and the key interaction sites of the synthesized MAO-B inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：6486 / 6496

页数：11

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