Synthesis and Biological Evaluation of Vitamin D3 Metabolite 20S,23S-Dihydroxyvitamin D3 and Its 23R Epimer

J Med Chem. 2016 May 26;59(10):5102-8. doi: 10.1021/acs.jmedchem.6b00182. Epub 2016 Apr 22.

Abstract

The vitamin D3 metabolite, 20S,23S-dihydroxyvitamin D3, was chemically synthesized for the first time and identified to be the same as the enzymatically produced metabolite. The C23 absolute configurations of both 20S,23S/R-dihydroxyvitamin D3 epimers were unambiguously assigned by NMR and Mosher ester analysis. Their kinetics of CYP27B1 metabolism were investigated during the production of their 1α-hydroxylated derivatives. Bioactivities of these products were compared in terms of vitamin D3 receptor activation, anti-inflammatory, and antiproliferative activities.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cholecalciferol / analogs & derivatives
  • Cholecalciferol / chemistry
  • Cholecalciferol / metabolism*
  • Dihydroxycholecalciferols / chemistry
  • Dihydroxycholecalciferols / metabolism
  • Dihydroxycholecalciferols / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / immunology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • 20,23-dihydroxyvitamin D3
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Dihydroxycholecalciferols
  • Receptors, Immunologic
  • leukocyte-associated immunoglobulin-like receptor 1
  • Cholecalciferol