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  • Mur ligase F as a new target for the flavonoids quercitrin, myricetin, and (–)-epicatechin
    Hrast, Martina ...
    MurC, D, E, and F are ATP-dependent ligases involved in the stepwise assembly of the tetrapeptide stem of forming peptidoglycan. As highly conserved targets found exclusively in bacterial cells, they ... are of significant interest for antibacterial drug discovery. In this study, we employed a computer-aided molecular design approach to identify potential inhibitors of MurF. A biochemical inhibition assay was conducted, screening twenty-four flavonoids and related compounds against MurC-F, resulting in the identification of quercitrin, myricetin, and (-)-epicatechin as MurF inhibitors with IC50 values of 143 µM, 139 µM, and 92 µM, respectively. Notably, (-)-epicatechin demonstrated mixed type inhibition with ATP and uncompetitive inhibition with D-Ala-D-Ala dipeptide and UM3DAP substrates. Furthermore, in silico analysis using Sitemap and subsequent docking analysis using Glide revealed two plausible binding sites for (-)-epicatechin. The study also investigated the crucial structural features required for activity, with a particular focus on the substitution pattern and hydroxyl group positions, which were found to be important for the activity. The study highlights the significance of computational approaches in targeting essential enzymes involved in bacterial peptidoglycan synthesis.
    Source: Journal of computer-aided molecular design. - ISSN 0920-654X (Vol. 37, iss. 12, 2023, str. 721-733)
    Type of material - article, component part ; adult, serious
    Publish date - 2023
    Language - english
    COBISS.SI-ID - 167509251

    Link(s):

    https://link.springer.com/article/10.1007/s10822-023-00535-z
    Repository of the University of Ljubljana – RUL
    DOI

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