Selective DNA Gyrase Inhibitors: Multi-Target in Silico Profiling with 3D-Pharmacophores.

ABSTRACT: DNA gyrase is an important target for the development of novel antibiotics. Although ATP-competitive DNA gyrase (GyrB) inhibitors are a well-studied class of antibacterial agents, there is currently no representative used in therapy, largely due to unwanted off-target activities. Selectivity of GyrB inhibitors against closely related human ATP-binding enzymes should be evaluated early in development to avoid off-target binding to homologous binding domains. To address this challenge, we developed selective 3D-pharmacophore models for GyrB, human topoisomerase IIα (TopoII), and the Hsp90 N-terminal domain (NTD) to be used in in silico activity profiling paradigms to identify molecules selective for GyrB over TopoII and Hsp90, as starting points for hit expansion and lead optimization. The m

SUBMITTER: Tomasic T 

PROVIDER: S-EPMC8400042 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature