Fiche publication
Date publication
juin 2024
Journal
Journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROCHEL-GUIBERTEAU Natacha
Tous les auteurs :
Gómez-Bouzó U, Peluso-Iltis C, Santalla H, Quevedo MA, Verlinden L, Verstuyf A, Fall Y, Gómez G, Rochel N
Lien Pubmed
Résumé
We synthesized two new gemini analogues, and , that incorporate a modified longer side chain containing a cyclopropane group. The evaluation of the bioactivities of the two gemini analogues indicated that the 17,20 threo (20) compound, , is the most active one and is as active as 1,25(OH)D. Docking and molecular dynamics (MD) data showed that the compounds bind efficiently to vitamin D receptor (VDR) with to form an energetically more favorable interaction with His397. Structural analysis indicated that whereas the compound efficiently stabilizes the active VDR conformation, it induces conformational changes in the H6-H7 VDR region that are greater than those induced by the parental Gemini and that this is due to the occupancy of the secondary channel by its modified side chain.
Référence
J Med Chem. 2024 06 10;:
