Pharmacophore modeling, docking and the integrated use of a ligand- and structure-based virtual screening approach for novel DNA gyrase inhibitors: synthetic and biological evaluation studies.

ABSTRACT: Fluoroquinolones, a class of compound, act via inhibiting DNA gyrase and topoisomerase IV enzymes. This is an important class of drugs with high success rates for the treatment of tuberculosis and other bacterial infections. An indirect drug design approach was used to develop a meaningful pharmacophore model using the HypoGen module of Discovery Studio 2.0 on a set of 27 structurally diverse compounds with a wide range of biological activity (5 log units). The best hypothesis had three hydrogen bond acceptors (HBA) and one hydrophobic (Hy) moiety, showing r = 0.95, and it predicts the test set of 44 compounds well, with r ² = 0.823. The same features (acceptor and hydrophobic functionality) were validated at the binding site of the DNA gyrase active site us

SUBMITTER: Mathpal D 

PROVIDER: S-EPMC9042709 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature