Synthesis of a dansyl-labeled inhibitor of 17β-hydroxysteroid dehydrogenase type 3 for optical imaging

Bioorg Med Chem Lett. 2016 May 1;26(9):2179-83. doi: 10.1016/j.bmcl.2016.03.069. Epub 2016 Mar 17.

Abstract

The steroidogenic enzyme 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a therapeutic target in the management of androgen-sensitive diseases such as prostate cancer and benign prostate hyperplasia. In this Letter, we designed and synthesized the first fluorescent inhibitor of this enzyme by combining a fluorogenic dansyl moiety to the chemical structure of a known inhibitor of 17β-HSD3. The synthesized compound 3 is a potent fluorogenic compound (λex=348 nm and λ em=498 nm). It crosses the cell membrane, keeps its fluorescent properties and is distributed inside the LNCaP cells overexpressing 17β-HSD3, where it inhibits the transformation of 4-androstene-3,17-dione into the androgen testosterone (IC50=262 nM).

Keywords: Dansyl; Fluorescent agent; Hydroxysteroid dehydrogenase; Inhibitor; Steroid.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
  • Androstanes / chemical synthesis
  • Androstanes / pharmacology*
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Dansyl Compounds / chemical synthesis
  • Dansyl Compounds / pharmacology*
  • Flow Cytometry
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / pharmacology*
  • Humans
  • Sulfonamides / chemical synthesis
  • Sulfonamides / pharmacology

Substances

  • Androstanes
  • Dansyl Compounds
  • Fluorescent Dyes
  • Sulfonamides
  • 17-Hydroxysteroid Dehydrogenases
  • 17beta-hydroxysteroid dehydrogenase type 3