Retiferols – synthesis and biological activity of a conceptually novel class of vitamin D analogs. (June 2014)

• Record Type: Journal Article
• Authors: Bolla, Narasimha Rao; Marcinkowska, Ewa; Brown, Geoffrey; Kutner, Andrzej
• Is Part Of: Expert opinion on therapeutic patents. Volume 24:Number 6(2014:Jun.)
• Page Start: 633
• Page End: 646
• Publication Date: 2014-06
• Subjects: Drugs -- Patents -- Periodicals; 615.10272
• DOI: 10.1517/13543776.2014.898061
• Languages: English
• ISSNs: 1354-3776

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> 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.</p> <p> <bold> <italic>Areas covered:</italic> </bold> 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.</p> <p> <bold> <italic>Expert opinion:</italic> </bold> 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.</p> </abstract>