In silico discovery of 2-amino-4-(2,4-dihydroxyphenyl)thiazoles as novel inhibitors of DNA gyrase B

Matjaz Brvar; Andrej Perdih; Marko Oblak; Lucija Peterlin Masic; Tom Solmajer

doi:10.1016/j.bmcl.2009.12.060

In silico discovery of 2-amino-4-(2,4-dihydroxyphenyl)thiazoles as novel inhibitors of DNA gyrase B

Bioorg Med Chem Lett. 2010 Feb 1;20(3):958-62. doi: 10.1016/j.bmcl.2009.12.060. Epub 2009 Dec 22.

Authors

Matjaz Brvar¹, Andrej Perdih, Marko Oblak, Lucija Peterlin Masic, Tom Solmajer

Affiliation

¹ National Institute of Chemistry, Hajdrihova 19, 1001 Ljubljana, Slovenia.

PMID: 20045642
DOI: 10.1016/j.bmcl.2009.12.060

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites / physiology
DNA Gyrase / metabolism
Drug Discovery / methods*
Structure-Activity Relationship
Thiazoles / chemistry*
Thiazoles / metabolism
Thiazoles / pharmacology*
Topoisomerase II Inhibitors*

Substances

Thiazoles
Topoisomerase II Inhibitors
DNA Gyrase