VSE knjižnice (vzajemna bibliografsko-kataložna baza podatkov COBIB.SI)
  • New N-phenyl-4,5-dibromopyrrolamides and N-phenylindolamides as ATPase inhibitors of DNA gyrase
    Zidar, Nace ...
    Following the withdrawal of novobiocin, the introdu ction of a new ATPase inhibitor of DNA gyrase to the clinic would add the first repres entative of this mechanistic class to the antibacterial ... pipeline. This would be of great impo rtance because of the well-known problems associated with antibacterial resistance. Using str ucture-based design and starting from the recently determined crystal structure of the N -phenyl-4,5-dibromopyrrolamide inhibitor-DNA gyrase B complex, we have prepared 28 new N -phenyl-4,5-dibromopyrrolamides and N - phenylindolamides and evaluated them against DNA gy rase from Escherichia coli . The most potent compound was 2-((4-(4,5-dibromo-1 H -pyrrole-2-carboxamido)phenyl)amino)-2- oxoacetic acid ( 9a ), with an IC 50 of 0.18 micro M against E. coli gyrase. A selected set of compounds was evaluated against DNA gyrase from Staphylococcus aureus and against topoisomerase IV from E. coli and S. aureus , but the activities were weaker. The binding affinity of 2-((4-(4,5-dibromo-1 H -pyrrole-2-carboxamido)phenyl)amino)-2-oxoacetic ac id ( 9a ) to E. coli gyrase was studied using surface plasmon resonance . In the design of the present series, the focus was on the optimisation o f biological activities of compounds especially by varying their size, the position and orientation of key functional groups, and their acid-base properties. The structure-activity relationship (SAR) was examined and the results were rationalised with molecular docking.
    Vir: European journal of medicinal chemistry. - ISSN 0223-5234 (Vol. 117, 2016, str. 197-211)
    Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasle
    Leto - 2016
    Jezik - angleški
    COBISS.SI-ID - 4050801

    Povezava(-e):

    http://www.sciencedirect.com/science/article/pii/S022352341630263X

    Dostop preko računalnikov UL


    DOI

Vnos na polico