In silico fragment-based discovery of indolin-2-one analogues as potent DNA gyrase inhibitors.
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 24kDa N-terminal fragment of DNA gyrase B. Further in silico optimization of indolin-2-one led to the discovery of potent DNA gyrase inhibitors.
Oblak
Marko
M
National Institute of Chemistry, Laboratory for Molecular Modelling and NMR Spectroscopy, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.
Grdadolnik
Simona Golic
SG
Kotnik
Miha
M
Jerala
Roman
R
Filipic
Metka
M
Solmajer
Tomaz
T
D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D059005:Topoisomerase II Inhibitors
D004791:Enzyme Inhibitors; D007211:Indoles; D059005:Topoisomerase II Inhibitors; C456900:indolin-2-one