Design, synthesis and evaluation of side-chain hydroxylated derivatives of lithocholic acid as potent agonists of the vitamin D receptor (VDR).

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

https://www.ncbi.nlm.nih.gov/pubmed/34339974

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