Design, synthesis and biological evaluation of novel nitroaromatic compounds as potent glutathione reductase inhibitors

被引：50

作者：

Cakmak, Resit ^{[2
,3
]}

Durdagi, Serdar ^{[4
]}

Ekinci, Deniz ^{[1
]}

Senturk, Murat ^{[5
]}

Topal, Giray ^{[3
,6
]}

机构：

[1] Ondokuz Mayis Univ, Fac Agr, Agr Biotechnol Dept, Samsun, Turkey

[2] Batman Univ, Sci & Art Fac, Dept Chem, Batman, Turkey

[3] Dicle Univ, Dept Chem, Ziya Gokalp Educ Fac, Diyarbakir, Turkey

[4] Univ Calgary, Dept Biol Sci, Inst Biocomplex & Informat, Calgary, AB T2N 1N4, Canada

[5] Ibrahim Cecen Univ Agri, Sci & Art Fac, Dept Chem, Agri, Turkey

[6] Batman Univ, Tech Educ Fac, Batman, Turkey

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 18期

关键词：

Glutathione reductase; Antimalaria; Nitroaromatic; In silico docking; DRUGS; CHLOROQUINE; DEGRADATION; MECHANISM; HEME;

D O I：

10.1016/j.bmcl.2011.07.002

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Discovery of GR inhibitors has become very popular recently due to antimalarial and anticancer activities. In this study, the synthesis and GR inhibitory capacities of novel nitroaromatic compounds (NCs) (1-3) were reported. Some commercially available molecules were also tested for comparison reasons. The novel NCs were obtained in high yields using simple chemical procedures and exhibited much potent inhibitory activities against GR at low micromolar concentrations with K-i values ranging from 0.211 to 4.57 mu M as compared with well-known agents. Inhibition mechanism was assessed as being due to occlusion of the active site entrance by means of the NCs. Molecular docking results have shown that docking poses of ligands are able to construct binding interactions with the essential amino acids. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：5398 / 5402

页数：5

共 29 条

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