Design, Synthesis, Computational and Biological Evaluation of Novel Structure Fragments Based on Lithocholic Acid (LCA).
Takeda G protein-coupled receptor 5 (TGR5)
bile acids
hydrophilicity
luciferase-based reporter assay
metabolic disorders
structure–activity relationship (SAR)
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
11 Jul 2023
11 Jul 2023
Historique:
received:
07
03
2023
revised:
30
06
2023
accepted:
07
07
2023
medline:
31
7
2023
pubmed:
29
7
2023
entrez:
29
7
2023
Statut:
epublish
Résumé
The regulation of bile acid pathways has become a particularly promising therapeutic strategy for a variety of metabolic disorders, cancers, and diseases. However, the hydrophobicity of bile acids has been an obstacle to clinical efficacy due to off-target effects from rapid drug absorption. In this report, we explored a novel strategy to design new structure fragments based on lithocholic acid (LCA) with improved hydrophilicity by introducing a polar "oxygen atom" into the side chain of LCA, then (i) either retaining the carboxylic acid group or replacing the carboxylic acid group with (ii) a diol group or (iii) a vinyl group. These novel fragments were evaluated using luciferase-based reporter assays and the MTS assay. Compared to LCA, the result revealed that the two lead compounds
Identifiants
pubmed: 37513205
pii: molecules28145332
doi: 10.3390/molecules28145332
pmc: PMC10383687
pii:
doi:
Substances chimiques
Lithocholic Acid
5QU0I8393U
Bile Acids and Salts
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wanek Family Project
ID : 2011440
Organisme : The National Institutes of Health grants
ID : R01DK124627 to W.H. and COH P30CA33572 to COH
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