In silico fragment-based discovery of indolin-2-one analogues as potent DNA gyrase inhibitors

被引:75
作者
Oblak, M
Grdadolnik, SG
Kotnik, M
Jerala, R
Filipic, M
Solmajer, T
机构
[1] Natl Inst Chem, Lab Mol Modelling & NMR Spect, SI-1001 Ljubljana, Slovenia
[2] Lek Pharmaceut dd, Drug Discovery, SI-1526 Ljubljana, Slovenia
[3] Natl Inst Chem, Biotechnol Lab, SI-1001 Ljubljana, Slovenia
[4] Natl Inst Biol, Dept Genet Toxicol & Canc Biol, SI-1001 Ljubljana, Slovenia
关键词
DNA gyrase B inhibitors; virtual screening; indolin-2-one;
D O I
10.1016/j.bmcl.2005.08.068
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
We describe here the fragment-based design of potent DNA gyrase inhibitors. Using the tools of virtual screening and NMR spectroscopy we identified the binding of two low-molecular weight fragments (2-aminobenzimidazole and indolin-2-one) to the 24 kDa N-terminal fragment of DNA gyrase B. Further in silico optimization of indolin-2-one led to the discovery of potent DNA gyrase inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5207 / 5210
页数:4
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