Pregnenolonyl-α-glucoside exhibits marked anti-cancer and CYP17A1 enzymatic inhibitory activities

Chem Commun (Camb). 2020 Feb 6;56(11):1733-1736. doi: 10.1039/c9cc09415f.

Abstract

We report here that pregnenolonyl-α-glucoside (2), a steryl glycoside synthesized directly from pregnenolone and glucose via a consecutive multienzyme-catalyzed process, exhibits marked dose-dependent cytotoxic activity against HT29, AGS, and ES-2 cells with IC50 values of 23.5 to 50.9 μM. An in vitro CYP17A1 binding pattern assay and protein-ligand docking model support that 2, like abiraterone, binds in the active site heme iron pocket of CYP17A1.

MeSH terms

  • Androstenes / metabolism
  • Androstenes / pharmacology
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Bacteria / enzymology
  • Catalytic Domain
  • Cell Line, Tumor
  • Cytochrome P-450 Enzyme Inhibitors / chemistry
  • Cytochrome P-450 Enzyme Inhibitors / metabolism
  • Cytochrome P-450 Enzyme Inhibitors / pharmacology*
  • Glucosides / chemical synthesis
  • Glucosides / metabolism
  • Glucosides / pharmacology*
  • Glycosylation
  • HEK293 Cells
  • Humans
  • Molecular Docking Simulation
  • Pregnenolone / analogs & derivatives*
  • Pregnenolone / metabolism
  • Pregnenolone / pharmacology*
  • Protein Binding

Substances

  • Androstenes
  • Antineoplastic Agents
  • Cytochrome P-450 Enzyme Inhibitors
  • Glucosides
  • Pregnenolone
  • abiraterone