title: In silico fragment-based discovery of indolin-2-one analogues as potent DNA gyrase inhibitors.
abstract: 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.
authors.affiliation: National Institute of Chemistry, Laboratory for Molecular Modelling and NMR Spectroscopy, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.
authors.forename: Marko
authors.initials: M
authors.lastname: Oblak
authors.forename: Simona Golic
authors.initials: SG
authors.lastname: Grdadolnik
authors.forename: Miha
authors.initials: M
authors.lastname: Kotnik
authors.forename: Roman
authors.initials: R
authors.lastname: Jerala
authors.forename: Metka
authors.initials: M
authors.lastname: Filipic
authors.forename: Tomaz
authors.initials: T
authors.lastname: Solmajer
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D059005:Topoisomerase II Inhibitors; C456900:indolin-2-one