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.
Original language | English |
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Pages (from-to) | 633-646 |
Number of pages | 14 |
Journal | Expert Opinion on Therapeutic Patents |
Volume | 24 |
Issue number | 6 |
Early online date | 22 Mar 2014 |
DOIs | |
Publication status | Published - 2014 |
Keywords
- Animals
- Drug Design
- Humans
- Models, Molecular
- Molecular Docking Simulation
- Receptors, Calcitriol
- Structure-Activity Relationship
- Vitamin D