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  • Refining the structure - activity relationships of 2-phenylcyclopropane carboxylic acids as inhibitors of O-acetylserine sulfhydrylase isoforms [Elektronski vir]
    Magalhães, Joana ...
    The lack of efficacy of current antibacterials to treat multidrug resistant bacteria poses a life-threatening alarm. In order to develop enhancers of the antibacterial activity, we carried out a ... medicinal chemistry campaign aiming to develop inhibitors of enzymes that synthesise cysteine and belong to the reductive sulphur assimilation pathway, absent in mammals. Previous studies have provided a novel series of inhibitors for O-acetylsulfhydrylase % a key enzyme involved in cysteine biosynthesis. Despite displaying nanomolar affinity, the most active representative of the series was not able to interfere with bacterial growth, likely due to poor permeability. Therefore, we rationally modified the structure of the hit compound with the aim of promoting their passage through the outer cell membrane porins. The new series was evaluated on the recombinant enzyme from Salmonella enterica serovar Typhimurium, with several compounds able to keep nanomolar binding affinity despite the extent of chemical manipulation.
    Source: Journal of enzyme inhibition and medicinal chemistry. - ISSN 1475-6374 (Vol. 34, iss. 1, 2019, str. 31-43)
    Type of material - e-article ; adult, serious
    Publish date - 2019
    Language - english
    COBISS.SI-ID - 80276227

    Link(s):

    https://www.tandfonline.com/doi/full/10.1080/14756366.2018.1518959
    DOI

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