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  • Psoralen derivatives as inhibitors of mycobacterium tuberculosis proteasome [Elektronski vir]
    Rožman, Kaja, farmacevtka ...
    Protein degradation is a fundamental process in all living organisms. An important part of this system is a multisubunit, barrel-shaped protease complex called the proteasome. This enzyme is directly ... responsible for the proteolysis of ubiquitin- or pup-tagged proteins to smaller peptides. In this study, we present a series of 92 psoralen derivatives, of which 15 displayed inhibitory potency against the Mycobacterium tuberculosis proteasome in low micromolar concentrations. The best inhibitors, i.e., 8, 11, 13 and 15, exhibited a mixed type of inhibition and overall good inhibitory potency in biochemical assays. N-(cyanomethyl)acetamide 8 (Ki = 5.6 microM) and carboxaldehyde-based derivative 15 (Ki = 14.9 microM) were shown to be reversible inhibitors of the enzyme. On the other hand, pyrrolidine-2,5-dione esters 11 and 13 irreversibly inhibited the enzyme with Ki values of 4.2 microM and 1.1 microM, respectively. In addition, we showed that an established immunoproteasome inhibitor, PR-957, is a noncompetitive irreversible inhibitor of the mycobacterial proteasome (Ki = 5.2 % 1.9 microM, kinact/Ki = 96 % 41 M%1%s%1). These compounds represent interesting hit compounds for further optimization in the development of new drugs for the treatment of tuberculosis.
    Vir: Molecules [Elektronski vir]. - ISSN 1420-3049 (Vol. 25, no. 6, 2020, str. 1-14)
    Vrsta gradiva - e-članek ; neleposlovje za odrasle
    Leto - 2020
    Jezik - angleški
    COBISS.SI-ID - 4894321

    Povezava(-e):

    https://www.mdpi.com/1420-3049/25/6/1305

    Odprt dostop


    Repozitorij Univerze v Ljubljani – RUL
    DOI

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