title: Retiferols - synthesis and biological activity of a conceptually novel class of vitamin D analogs.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmaceutical Research Institute , 8 Rydygiera, Warsaw 02-785 , Poland a.kutner@ifarm.eu.
authors.forename: Narasimha Rao
authors.initials: NR
authors.lastname: Bolla
authors.forename: Ewa
authors.initials: E
authors.lastname: Marcinkowska
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Brown
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kutner
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D
keywords: RAD2; all-trans-retinoic acid; psoriasis; retiferol; vitamin D analogs; vitamin D receptor