These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Design, synthesis and biological evaluation of novel Pseudomonas aeruginosa DNA gyrase B inhibitors.
    Author: Jogula S, Krishna VS, Meda N, Balraju V, Sriram D.
    Journal: Bioorg Chem; 2020 Jul; 100():103905. PubMed ID: 32388436.
    Abstract:
    In the present study, we attempted to develop a novel class of compounds active against Pseudomonas aeruginosa (Pa) by exploring the pharmaceutically well exploited enzyme targets. Since, lack of Pa gyrase B crystal structures, Thermus thermophilus gyrase B in complex with novobiocin (1KIJ) was used as template to generate model structure by performing homology modeling. Further the best model was validated and used for high-throughput virtual screening, docking and dynamics simulations using the in-house database for identification of Pa DNA gyrase B inhibitors. This study led to an identification of three lead molecules with IC50 values in range of 6.25-15.6 µM against Pa gyrase supercoiling assay. Lead-1 optimization and expansion resulted in 15 compounds. Among the synthesized compounds six compounds were shown good enzyme inhibition than Lead-1 (IC50 6.25 µM). Compound 13 emerged as the most potential compound exhibiting inhibition of Pa gyrase supercoiling with an IC50 of 2.2 µM; and in-vitro Pa activity with MIC of 8 µg/mL in presence of efflux pump inhibitor; hence could be further developed as novel inhibitor for Pa gyrase B.
    [Abstract] [Full Text] [Related] [New Search]