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Docking and antibacterial activity of novel nontoxic 5-arylidenepyrimidine-triones as inhibitors of NDM-1 and MetAP-1

    Roman S Tumskiy

    *Author for correspondence:

    E-mail Address: tumskiy_r@ibppm.ru

    Institute of Biochemistry & Physiology of Plants & Microorganisms, Russian Academy of Sciences, 13 Prospekt Entuziastov, Saratov, 410049, Russia

    ,
    Anastasiia V Tumskaia

    Chemistry Institute, Saratov State University, 83 Astrakhanskaya, Saratov, 410012, Russia

    ,
    Timophey E Pylaev

    Institute of Biochemistry & Physiology of Plants & Microorganisms, Russian Academy of Sciences, 13 Prospekt Entuziastov, Saratov, 410049, Russia

    Saratov State Medical University n.a. V.I. Razumovsky, 112 Bolshaya Kazachya St., Saratov, 410012, Russia

    ,
    Elena S Avdeeva

    Institute of Biochemistry & Physiology of Plants & Microorganisms, Russian Academy of Sciences, 13 Prospekt Entuziastov, Saratov, 410049, Russia

    &
    Stella S Evstigneeva

    Institute of Biochemistry & Physiology of Plants & Microorganisms, Russian Academy of Sciences, 13 Prospekt Entuziastov, Saratov, 410049, Russia

    Published Online:https://doi.org/10.4155/fmc-2021-0020

    Background: Antibiotic resistance, which occurs through the action of metallo-β-lactamases (NDM-1), is a serious problem in the treatment of infectious diseases. Therefore, the discovery of new NDM-1 inhibitors and promising antibacterial agents as inhibitors of alternative targets (MetAP-1) is important. Method & results: In this study, a virtual library of 5-arylidene barbituric acids was created and molecular docking was performed for identification of novel possible inhibitors of NDM-1 and MetAP-1. Antibacterial activity (agar well-diffusion assay) and cytotoxicity (alamarBlue assay) of perspective compounds were evaluated. Pharmacokinetic profiles and molecular properties were predicted. Conclusion: We have identified possible novel inhibitors of NDM-1 and MetAP-1 with bacteriostatic activity, most of which are not cytotoxic and have potential excellent drug-likeness properties.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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