Synthesis, structure, and biological activity of des-side chain analogues of 1alpha,25-dihydroxyvitamin D3 with substituents at C18.
Fiche publication
Date publication
mai 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MORAS Dino
Tous les auteurs :
Verlinden L, Verstuyf A, Eelen G, Bouillon R, Ordonez-Moran P, Larriba MJ, Munoz A, Rochel N, Sato Y, Moras D, Maestro M, Seoane S, Dominguez F, Eduardo-Canosa S, Nicoletti D, Moman E, Mourino A
Lien Pubmed
Résumé
An improved synthetic route to 1alpha,25-dihydroxyvitamin D(3) des-side chain analogues 2 a and 2 b with substituents at C18 is reported, along with their biological activity. These analogues display significant antiproliferative effects toward MCF-7 breast cancer cells and prodifferentiation activity toward SW480-ADH colon cancer cells; they are also characterized by a greatly decreased calcemic profile. The crystal structure of the human vitamin D receptor (hVDR) complexed to one of these analogues, 20(17-->18)-abeo-1alpha,25-dihydroxy-22-homo-21-norvitamin D(3) (2 a) reveals that the side chain introduced at position C18 adopts the same orientation in the ligand binding pocket as the side chain of 1alpha,25-dihydroxyvitamin D(3).
Référence
ChemMedChem. 2011 May 2;6(5):788-93