VSE knjižnice (vzajemna bibliografsko-kataložna baza podatkov COBIB.SI)
  • The overview of development of novel bacterial topoisomerase inhibitors effective against multidrug-resistant bacteria in an academic environment : from early hits to in vivo active antibacterials
    Zorman, Maša ...
    Antimicrobial resistance caused by the excessive and inappropriate use of antibacterial drugs is a global health concern. Currently, we are on a fine line between the fact that most bacterial ... infections can still be cured with the antibiotics known so far, and the emergence of infections with bacteria resistant to several drugs at the same time, against which we no longer have an effective drug. Therefore, new antibacterial drugs are urgently needed to curb the hard-to-treat infections. Our group has developed new antibacterials from the class of novel bacterial topoisomerase inhibitors (NBTIs) that exhibit broad-spectrum antibacterial activity. This article reviews our efforts in developing highly potent NBTIs over the past decade. Following the discovery of an initial hit with potent enzyme inhibitory and broad-spectrum antibacterial activity, an extensive hit-to-lead campaign was conducted with the goal of optimizing physicochemical properties, reducing hERG inhibition, and maintaining antibacterial activity against both Gram-positive and Gram-negative bacteria, with a focus on methicillin-resistant Staphylococcus aureus (MRSA). This optimization strategy resulted in an amide-containing, focused NBTI library with compounds exhibiting potent antibacterial activity against Gram-positive bacteria, reduced hERG inhibition, no cardiotoxicity in in vivo zebrafish model, and favorable in vivo efficacy in a neutropenic murine thigh infection model for MRSA infections.
    Vir: European Journal of Pharmaceutical Sciences. - ISSN 0928-0987 (Vol. 192, 2024, 7 str.)
    Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasle
    Leto - 2024
    Jezik - angleški
    COBISS.SI-ID - 171802883

    Povezava(-e):

    https://www.sciencedirect.com/science/article/pii/S0928098723002622
    DOI

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