Retiferols - synthesis and biological activity of a conceptually novel class of vitamin D analogs

Research output: Contribution to journalArticle

Authors

  • Narasimha Rao Bolla
  • Ewa Marcinkowska
  • Geoff Brown
  • Andrzej Kutner

Colleges, School and Institutes

Abstract

INTRODUCTION: The hypothesis that retiferols are a novel class of vitamin D analogs with therapeutic potential has been recently proved. The CD-ring of vitamin D, originated from a steroid precursor, is not necessary for biological activity. The retiferol, disubstituted at C-13, was bound to the ligand-binding domain (LBD) of vitamin D receptor (VDR) just like the vitamin D hormone [1,25-(OH)2D3]. This finding opens the way for retiferols as a novel class of vitamin D therapeutics.

AREAS COVERED: This review presents the concept of retiferols and their structure evolution. Medicinal chemistry and therapeutic perspective of retiferols are reviewed showing how these vitamin D analogs became a source of potential therapeutics.

EXPERT OPINION: Docking experiments and molecular modeling have shown that positioning of vitamin D analog at the LBD of VDR is not disturbed by deletion of a large portion of the vitamin D, exactly as hypothesized. Twenty years of structural modifications have shown that removal of the CD-ring fragment and regioselective methylation results in an almost complete loss of the undesired calcemic activity of retiferol while gaining the agonistic activity comparable to that of 1,25-(OH)2D3.

Details

Original languageEnglish
Pages (from-to)633-646
Number of pages14
JournalExpert Opinion on Therapeutic Patents
Volume24
Issue number6
Early online date22 Mar 2014
Publication statusPublished - 2014

Keywords

  • Animals, Drug Design, Humans, Models, Molecular, Molecular Docking Simulation, Receptors, Calcitriol, Structure-Activity Relationship, Vitamin D