In silico discovery of 2-amino-4-(2,4-dihydroxyphenyl)thiazoles as novel inhibitors of DNA gyrase B.
Cyclothialidines are a class of bacterial DNA gyrase B (GyrB) subunit inhibitors, targeting its ATP-binding site. Starting from the available structural information on cyclothialidine GR122222X (2), an in silico virtual screening campaign was designed combining molecular docking calculations with three-dimensional structure-based pharmacophore information. A novel class of 2-amino-4-(2,4-dihydroxyphenyl)thiazole based inhibitors (5-9) with low micromolar antigyrase activity was discovered.
Brvar
Matjaz
M
National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia.
Perdih
Andrej
A
Oblak
Marko
M
Masic
Lucija Peterlin
LP
Solmajer
Tom
T
D001665:Binding Sites / Q000502:physiology; D027081:DNA Gyrase / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
D013844:Thiazoles; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase