Steroid sulfatase inhibiting lanostane triterpenes - Structure activity relationship and in silico insights

Ulrike Grienke, Teresa Kaserer, Benjamin Kirchweger, George Lambrinidis, Ralph Kandel, Daniela Schuster, Emmanuel Mikros, Judith Maria Rollinger, Paul A Foster

    Publications: Contribution to journalArticlePeer Reviewed

    Abstract

    Steroid sulfatase (STS) transforms hormone precursors into active steroids. Thus, it represents a target of intense research regarding hormone-dependent cancers. In this study, three ligand-based pharmacophore models were developed to identify STS inhibitors from natural sources. In a pharmacophore-based virtual screening of a curated molecular TCM database, lanostane-type triterpenes (LTTs) were predicted as STS ligands. Three traditionally used polypores rich in LTTs, i.e., Ganoderma lucidum Karst., Gloeophyllum odoratum Imazeki, and Fomitopsis pinicola Karst., were selected as starting materials. Based on eighteen thereof isolated LTTs a structure activity relationship for this compound class was established with piptolinic acid D (1), pinicolic acid B (2), and ganoderol A (3) being the most pronounced and first natural product STS inhibitors with IC50 values between 10 and 16 µM. Molecular docking studies proposed crucial ligand target interactions and a prediction tool for these natural compounds correlating with experimental findings.
    Original languageEnglish
    Article number103495
    Number of pages10
    JournalBioorganic Chemistry
    Volume95
    DOIs
    Publication statusPublished - Jan 2020

    Austrian Fields of Science 2012

    • 104013 Natural product chemistry

    Keywords

    • DISCOVERY
    • ESTRONE SULFATASE
    • IROSUSTAT
    • Lanostane-type triterpenes
    • Molecular docking
    • PHARMACOPHORE
    • POTENT INHIBITORS
    • PROTEIN
    • Polypores
    • REVERSIBLE INHIBITORS
    • Steroid sulfatase
    • Virtual screening

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