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  • Amide containing NBTI antibacterials with reduced hERG inhibition, retained antimicrobial activity against gram-positive bacteria and in vivo efficacy
    Kokot, Maja, 1995- ...
    Novel bacterial topoisomerase inhibitors (NBTIs) are new promising antimicrobials for the treatment of multidrug-resistant bacterial infections. In recent years, many new NBTIs have been discovered, ... however most of them struggle with the same issue - the balance between antibacterial activity and hERG-related toxicity. We started a new campaign by optimizing the previous series of NBTIs, followed by the design and synthesis of a new, amide-containing focused NBTI library to reduce hERG inhibition and maintain antibacterial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This optimization strategy yielded the lead compound 12 that exhibits potent antibacterial activity against Gram-positive bacteria, reduced hERG inhibition, no cardiotoxicity in zebrafish model, and a favorable in vivo efficacy in a neutropenic murine thigh infection model of MRSA infection.
    Source: European journal of medicinal chemistry. - ISSN 0223-5234 (Vol. 250, 2023, str. 1-13)
    Type of material - article, component part ; adult, serious
    Publish date - 2023
    Language - english
    COBISS.SI-ID - 141418755

    Link(s):

    https://www.sciencedirect.com/science/article/pii/S0223523423000752
    Repository of the University of Ljubljana – RUL
    DOI

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