Filamenting temperature-sensitive mutant Z inhibitors from Glycyrrhiza glabra and their inhibitory mode of action

Takashi Matsui, Subehan Lallo, Khoirun Nisa, Hiroyuki Morita

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)

    Abstract

    FtsZ is an essential protein for bacterial cell division, and an attractive and underexploited novel antibacterial target protein. Screening of Indonesian plants revealed the inhibitory activity of the methanol extract of Glycyrrhiza glabra on the Bacillus subtilis FtsZ (BsFtsZ) GTPase, and further bioassay-guided fractionation of the active methanol extract led to the isolation of seven known polyketides (1–7). Among them, gancaonin I (1), glycyrin (3), and isolicoflavanol (5) exhibited anti-BsFtsZ GTPase activities, at levels comparable to that of the synthetic FtsZ inhibitor, Zantrin Z3. Enzymatic assays using a BsFtsZ Val307R mutant protein and in silico simulations suggested that 1, 3, and 5 bind to the cleft on BsFtsZ, as in the case of the previously reported uncompetitive FtsZ inhibitor, PC190723, and thereby display their significant anti-BsFtsZ inhibitory activities. Furthermore, 1 also showed significant inhibitory activity against B. subtilis, with a MIC value of 5 μM. The present study provides new insights into the naturally occurring B. subtilis growth inhibitors.

    Original languageEnglish
    Pages (from-to)1420-1424
    Number of pages5
    JournalBioorganic and Medicinal Chemistry Letters
    Volume27
    Issue number6
    DOIs
    Publication statusPublished - 2017

    Keywords

    • Antibacterials
    • Docking simulation
    • FtsZ inhibitor
    • Glycyrrhiza glabra

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Pharmaceutical Science
    • Drug Discovery
    • Clinical Biochemistry
    • Organic Chemistry

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