Design, synthesis and evaluation of side-chain hydroxylated derivatives of lithocholic acid as potent agonists of the vitamin D receptor (VDR).
Fiche publication
Date publication
juillet 2021
Journal
Bioorganic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROCHEL-GUIBERTEAU Natacha
Tous les auteurs :
González CM, Gaikwad S, Lasanta G, Loureiro J, Nilsson N, Peluso-Iltis C, Rochel N, Mouriño A
Lien Pubmed
Résumé
A high number of biologically active and low-calcemic secosteroidal ligands of the vitamin D receptor (VDR) have been developed, some of which are already used clinically although with limited success in the treatment of hyperproliferative diseases because the required pharmaceutical dosages induce toxicity. We describe here the in silico design, synthesis, structural analysis and biological evaluation of two novel active lithocholic acid derivatives hydroxylated at the side chain as highly potent inhibitors of atopic dermatitis-relevant keratinocyte inflammation of potential therapeutic interest.
Mots clés
In silico design, Lithocholic acid derivatives, Stereoselective synthesis, Structure-function, Transcription, VDR agonist, Vitamin D receptor
Référence
Bioorg Chem. 2021 Jul 22;115:105202