Retiferols - synthesis and biological activity of a conceptually novel class of vitamin D analogs
Research output: Contribution to journal › Article
Colleges, School and Institutes
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.
|Number of pages||14|
|Journal||Expert Opinion on Therapeutic Patents|
|Early online date||22 Mar 2014|
|Publication status||Published - 2014|
- Animals, Drug Design, Humans, Models, Molecular, Molecular Docking Simulation, Receptors, Calcitriol, Structure-Activity Relationship, Vitamin D