The first locked side-chain analogues of calcitriol (1alpha,25-dihydroxyvitamin D3) induce vitamin D receptor transcriptional activity

Org Lett. 2003 Oct 30;5(22):4033-6. doi: 10.1021/ol0351246.

Abstract

[structure: see text]. We describe the synthesis of the first locked side-chain analogues of the natural hormone 1alpha,25-(OH)2-D3 and their effects on gene transcription in human colon cancer cells. Analogue 2 was more potent than 1alpha,25-(OH)2-D3 at inducing vitamin D receptor (VDR) transcriptional activity. Analogues 3a and 3b show potency similar to that of 1alpha,25-(OH)2-D3, whereas 3c was less active. The novel analogues efficiently bind VDR in vivo to induce transcription from a consensus vitamin D responsive element (VDRE).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Calcitriol / analogs & derivatives*
  • Calcitriol / chemistry
  • Calcitriol / pharmacology
  • Cell Line, Tumor / drug effects
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hydrocarbons, Aromatic / chemistry
  • Luciferases / analysis
  • Luciferases / genetics
  • Molecular Structure
  • Receptors, Calcitriol / agonists*
  • Receptors, Calcitriol / physiology
  • Structure-Activity Relationship
  • Transcription, Genetic / drug effects*
  • Vitamin D Response Element / genetics

Substances

  • Alkynes
  • Hydrocarbons, Aromatic
  • Receptors, Calcitriol
  • Luciferases
  • Calcitriol