title: In silico discovery and biophysical evaluation of novel 5-(2-hydroxybenzylidene) rhodanine inhibitors of DNA gyrase B.
abstract: Bacterial DNA gyrase is an established and validated target for the development of novel antibacterials. In our previous work, we identified a novel series of bacterial gyrase inhibitors from the class of 4-(2,4-dihydroxyphenyl) thiazoles. Our ongoing effort was designated to search for synthetically more available compounds with possibility of hit to lead development. By using the virtual screening approach, new potential inhibitors were carefully selected from the focused chemical library and tested for biological activity. Herein we report on a novel class of 5-(2-hydroxybenzylidene) rhodanines as gyrase B inhibitors with activity in low micromolar range and moderate antibacterial activity. The binding of the two most active compounds to the enzyme target was further characterised using surface plasmon resonance (SPR) and differential scanning fluorimetry methods (DSF).
authors.affiliation: National Institute of Chemistry, Laboratory for Biocomputing and Bioinformatics, Hajdrihova 19, 1001 Ljubljana, Slovenia.
authors.forename: Matjaž
authors.initials: M
authors.lastname: Brvar
authors.forename: Andrej
authors.initials: A
authors.lastname: Perdih
authors.forename: Vesna
authors.initials: V
authors.lastname: Hodnik
authors.forename: Miha
authors.initials: M
authors.lastname: Renko
authors.forename: Gregor
authors.initials: G
authors.lastname: Anderluh
authors.forename: Roman
authors.initials: R
authors.lastname: Jerala
authors.forename: Tom
authors.initials: T
authors.lastname: Solmajer
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D027081:DNA Gyrase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D013293:Enterococcus faecalis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006193:Haemophilus influenzae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: C574555:5-(2-hydroxybenzylidene)rhodanine; D000900:Anti-Bacterial Agents; D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D012236:Rhodanine; D027081:DNA Gyrase