Synthesis of 3-alkyl enol mimics inhibitors of type II dehydroquinase: factors influencing their inhibition potency

被引：18

作者：

Blanco, Beatriz ^{[1
]}

Sedes, Antia ^{[1
]}

Peon, Antonio ^{[1
]}

Lamb, Heather ^{[2
]}

Hawkins, Alastair R. ^{[2
]}

Castedo, Luis ^{[3
]}

Gonzalez-Bello, Concepcion ^{[1
]}

机构：

[1] Univ Santiago de Compostela, Ctr Singular Invest Quim Biol & Mat Mol CIQUS, Santiago De Compostela 15782, Spain

[2] Univ Newcastle, Sch Med, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[3] Univ Santiago de Compostela, Fac Quim, Dept Quim Organ, Santiago De Compostela 15782, Spain

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2012年 / 10卷 / 18期

关键词：

NANOMOLAR COMPETITIVE INHIBITORS; MYCOBACTERIUM-TUBERCULOSIS; BIOLOGICAL EVALUATION; RATIONALIZATION; DESIGN; INTERMEDIATE; SIMULATION; PREDICTION; MECHANISM;

D O I：

10.1039/c2ob07081b

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Several 3-alkylaryl mimics of the enol intermediate in the reaction catalyzed by type II dehydroquinase were synthesized to investigate the effect on the inhibition potency of replacing the oxygen atom in the side chain by a carbon atom. The length and the rigidity of the spacer was also studied. The inhibitory properties of the reported compounds against type II dehydroquinase from Mycobacterium tuberculosis and Helicobacter pylori are also reported. The binding modes of these analogs in the active site of both enzymes were studied by molecular docking using GOLD 5.0 and dynamic simulations studies.

引用

页码：3662 / 3676

页数：15

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[11]

2-N

[12] A 2ND GENERATION FORCE-FIELD FOR THE SIMULATION OF PROTEINS, NUCLEIC-ACIDS, AND ORGANIC-MOLECULES [J].