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

Abstract

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.

• Authors: Carmen M González, Sunil Gaikwad, Gonzalo Lasanta, Julian Loureiro, Niclas Nilsson, Carole Peluso-Iltis, Natacha Rochel, Antonio Mouriño
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 115 Pg. 105202 (10 2021) ISSN: 1090-2120 [Electronic] United States
• PMID: 34339974 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Receptors, Calcitriol
• VDR protein, human
• Lithocholic Acid

Topics

• Dose-Response Relationship, Drug
• Drug Design
• Humans
• Hydroxylation
• Lithocholic Acid (chemical synthesis, chemistry, pharmacology)
• Molecular Structure
• Receptors, Calcitriol (agonists)
• Structure-Activity Relationship