Pharmacophore-Based Virtual Screening and Molecular Dynamics Simulation for Identification of a Novel DNA Gyrase B Inhibitor with Benzoxazine Acetamide Scaffold.

ABSTRACT: DNA gyrase B is one of the enzyme targets for antimicrobial drug development, and its absence in mammals makes it a suitable target for the creation of safe antibacterial drugs. We identified six novel hits as DNA gyrase B inhibitors in the present study by employing 3D-pharmacophore structure-based virtual screening. The lead compounds complied with drug-likeness rules and lacked toxicity. Compound 4 (ZINC32858011) showed the highest inhibitory activity with an IC₅₀ value of 6.3 ± 0.1 μM against the DNA gyrase enzyme. In contrast, the positive controls ciprofloxacin and novobiocin used in enzyme inhibition assay had IC₅₀ values of 14.4 ± 0.2 and 12.4 ± 0.2 μM, respectively. The molecular docking of the six hits demonstrated that compounds 1, 2, 4, and 6 had suitable

SUBMITTER: Elseginy SA 

PROVIDER: S-EPMC8756603 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature