Inhibition of monoamine oxidases by coumarin-3-acyl derivatives: biological activity and computational study

被引：97
作者：
Chimenti, F
Secci, D
Bolasco, A
Chimenti, P
Granese, A
Befani, O
Turini, P
Alcaro, S
Ortuso, F
机构：
[1] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Sostanze Biol Camente, I-00185 Rome, Italy
[2] Univ Roma La Sapienza, Dipartimento Sci Biochim A Rossi Fanelli, I-00185 Rome, Italy
[3] Univ Roma La Sapienza, CNR, Ctr Biol Mol, I-00185 Rome, Italy
[4] Univ Catanzaro, Dipartimento Sci Farmaco Biol Complesso Nint Barb, I-88021 Roccelletta Di Borgia, CZ, Italy
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 14期
关键词：
MAO-inhibitors; coumarin;
D O I：
10.1016/j.bmcl.2004.05.010
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of coumarin-3-acyl derivatives have been synthesized and investigated for the ability to inhibit selectively monoamine oxidases. The coumarin-3-carboxylic acids, 2a-e, proved to be reversible and selective inhibitors of the MAO-B isoform, displaying pIC(50) values of particular interest: 2a shows pIC(50) 7.76 and a selectivity index (pS.I.) 2.94 and 2b shows pIC(50) 7.72 and a pS.I. of 2.80. The coumarin-3-acyl chlorides 3a-e showed high pIC(50) values against both MAO-A and MAO-B isoforms, 3d being the highest against MAO-B with a pIC(50) value of 8.00. In order to rationalize the activity/selectivity results, molecular descriptors were generated. Further insight about enzyme-inhibitor interaction was obtained by docking experiments with the MAO-B isoform. (C) 2004 Elsevier Ltd. All rights reserved.
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收藏
页码：3697 / 3703
页数：7
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