Monoamine oxidase A and B inhibiting effect and molecular modeling of some synthesized coumarin derivatives

被引：23

作者：

Abdelhafez, Omaima M. ^{[1
]}

Amin, Kamelia M. ^{[2
]}

Ali, Hamed I. ^{[3
]}

Abdalla, Mohamed M. ^{[4
]}

Batran, Rasha Z. ^{[1
]}

机构：

[1] Natl Res Ctr, Chem Nat Prod Dept, Dokki, Egypt

[2] Cairo Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo, Egypt

[3] Helwan Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo, Egypt

[4] Mapco Pharmaceut Ind Balteim, Res Unit, Balteim, Egypt

来源：

NEUROCHEMISTRY INTERNATIONAL | 2013年 / 62卷 / 02期

关键词：

MAO-A and B; 7-Oxycoumarins; Acetohydrazides; Dioxopyrrolidines; Molecular modeling; MAO INHIBITORS; SELECTIVE INHIBITORS; PARKINSONS-DISEASE; RESOLUTION; INSIGHTS; POTENT;

D O I：

10.1016/j.neuint.2012.11.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

New series of bioactive 7-oxycoumarin derivatives were synthesized and tested for their in vitro and in vivo monoamine oxidase (MAO) A and B inhibitory effect. In vitro studies revealed exceptionally potent and selective MAO-A inhibitors with K-i values on a picomolar range. The acetohydrazide (3b) and the dioxopyrrolidine derivative (7b) showed the most potent in vitro and in vivo MAO inhibition activity. Moreover, molecular modeling study of the synthesized compounds into MAO-A (PDB: 2Z5X) and MAO-B (PDB: 2XFN) binding sites exhibited direct correlation between AutoDock binding affinity and% inhibition MAO-A (pM) and MAO-B (mu M). In addition, the results of in vivo MAO inhibiting properties (ED50) of the tested compounds revealed better direct correlation. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：198 / 209

页数：12

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