Steroid sulfatase inhibiting lanostane triterpenes – structure activity relationship and in silico insights

Research output: Contribution to journalArticle

Authors

  • Ulrike Grienke
  • Teresa Kaserer
  • Benjamin Kirchweger
  • George Lambrinidis
  • Ralph T. Kandel
  • Daniela Schuster
  • Emmanuel Mikros
  • Judith M Rollinger

Colleges, School and Institutes

External organisations

  • University of Vienna
  • University of Innsbruck
  • National and Kapodistrian University of Athens
  • Paracelsus Medical University Salzburg

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.

Details

Original languageEnglish
Article number103495
Number of pages10
JournalBioorganic Chemistry
Volume95
Early online date9 Dec 2019
Publication statusE-pub ahead of print - 9 Dec 2019

Keywords

  • Steroid sulfatase, Polypores, Lanostane-type triterpenes, Virtual screening, Molecular docking