Selective inhibition of monoamine oxidase A by hispidol
Selective inhibition of monoamine oxidase A by hispidol
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DOI：
10.1016/j.bmcl.2018.01.049
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发表时间：
2018-02-15
影响因子：
2.7
通讯作者：
Kim, Hoon
中科院分区：
文献类型：
--
作者：
Baek, Seung Cheol;Lee, Hyun Woo;Kim, Hoon
Hispidol是从大豆中分离得到的一种极光化合物，对重组人单胺氧化酶-A(MAO-A)的一种异构体有较强的选择性抑制作用，其IC50值为0.26mU M，对MAO-B的抑制作用较弱(IC50=2.45mU M)。Hispidol对MAO-A具有可逆性和竞争性抑制作用，其K-I值为0.10 mU M，其抑制效力远大于市售药物托洛沙酮(IC50=1.10 mU M)。对MAO-B也具有可逆性和竞争性抑制作用(K-I=0.51µM)。磺维A能有效抑制MAO-A(IC_(50)=4.16 mU/M)，但不能抑制MAO-B(IC_(50)=80 mU/M)。化学结构的比较表明，硫黄素的3‘-羟基可能会降低其对MAO-A和MAO-B的抑制活性。柔性对接模拟表明，组氨酸与MAO-A的结合亲和力(-9.1kcal/mol)大于其与MAO-B的亲和力(-8.7kcal/mol)。对接模拟显示，Hispidol绑定在MAO-A或MAO-B的主要口袋上。研究结果表明，组氨酸是一种有效的、选择性的、可逆的MAO-A抑制剂，可作为开发新型MAO-A可逆抑制剂的先导化合物。(C)2018爱思唯尔有限公司。保留所有权利。
Hispidol, an aurone, isolated from Glycine max Merrill, was found to potently and selectively inhibit an isoform of recombinant human monoamine oxidase-A (MAO-A), with an IC50 value of 0.26 mu M, and to inhibit MAO-B, but with lower potency (IC50 = 2.45 mu M). Hispidol reversibly and competitively inhibited MAO-A with a K-i value of 0.10 mu M with a potency much greater than toloxatone (IC50 = 1.10 mu M), a marketed drug. It also reversibly and competitively inhibited MAO-B (K-i = 0.51 mu M). Sulfuretin, an analog of hispidol, effectively inhibited MAO-A (IC50 = 4.16 mu M) but not MAO-B (IC50 > 80 mu M). A comparison of their chemical structures showed that the 3'-hydroxyl group of sulfuretin might reduce its inhibitory activities against MAO-A and MAO-B. Flexible docking simulation revealed that the binding affinity of hispidol for MAO-A (-9.1 kcal/mol) was greater than its affinity for MAO-B (-8.7 kcal/mol). The docking simulation showed hispidol binds to the major pocket of MAO-A or MAO-B. The findings suggest hispidol is a potent, selective, reversible inhibitor of MAO-A, and that it be considered a novel lead compound for development of novel reversible inhibitors of MAO-A. (C) 2018 Elsevier Ltd. All rights reserved.