@article{3021123,
    title = "Steroid sulfatase inhibiting lanostane triterpenes – Structure activity relationship and in silico insights",
    author = "Grienke, U. and Kaserer, T. and Kirchweger, B. and Lambrinidis, G. and Kandel, R.T. and Foster, P.A. and Schuster, D. and Mikros, E. and Rollinger, J.M.",
    journal = "Bioorganic Chemistry",
    year = "2020",
    volume = "95",
    publisher = "Academic Press Inc.",
    issn = "0045-2068, 1090-2120",
    doi = "10.1016/j.bioorg.2019.103495",
    keywords = "15alpha hydroxy trametenolic acid;  21 hydroxy lanosterol;  eburicodiol;  enzyme inhibitor;  ergosterol;  ergosterol peroxide;  fomefficinic acid b;  fomefficinic acid d;  ganoderol a;  ganoderol b;  gloeophyllin a;  gloeophyllin b;  gloeophyllin k;  gloeophyllin l;  irosustat;  pinicolic acid b;  piptolinic acid d;  steryl sulfatase;  trametenolic acid b;  triterpene derivative;  unclassified drug;  enzyme inhibitor;  lanosterol;  ligand;  steryl sulfatase;  STS protein, human;  triterpene, Article;  carbon nuclear magnetic resonance;  chemical structure;  chromatography;  column chromatography;  controlled study;  crystal structure;  enzyme inhibition;  enzyme structure;  fomitopsis pinicola;  Ganoderma lucidum;  gloeophyllum odoratum;  high performance liquid chromatography;  hydrogen bond;  molecular docking;  Monte Carlo method;  priority journal;  protein structure;  proton nuclear magnetic resonance;  structure activity relation;  ultra performance liquid chromatography;  Basidiomycetes;  chemistry;  Coriolaceae;  dose response;  human;  isolation and purification;  metabolism;  molecular model;  structure activity relation, Basidiomycota;  Coriolaceae;  Dose-Response Relationship, Drug;  Enzyme Inhibitors;  Humans;  Lanosterol;  Ligands;  Models, Molecular;  Molecular Structure;  Reishi;  Steryl-Sulfatase;  Structure-Activity Relationship;  Triterpenes",
    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. © 2019 Elsevier Inc."
}