A benzoxazole derivative as an inhibitor of anaerobic choline metabolism by human gut microbiota.
Journal
RSC medicinal chemistry
ISSN: 2632-8682
Titre abrégé: RSC Med Chem
Pays: England
ID NLM: 101759460
Informations de publication
Date de publication:
17 Dec 2020
17 Dec 2020
Historique:
received:
20
06
2020
accepted:
03
08
2020
entrez:
7
6
2021
pubmed:
8
6
2021
medline:
8
6
2021
Statut:
epublish
Résumé
Metabolic pathways mediated by human gut bacteria have emerged as potential therapeutic targets because of their association with the pathophysiology of various human diseases. The anaerobic transformation of choline into trimethylamine (TMA) by gut microbiota is directly linked to type 2 diabetes, fatty liver disease, and cardiovascular diseases. Structural analogs of choline have been developed as competitive inhibitors of choline TMA-lyase (CutC), a key enzyme for the conversion of choline to TMA. However, weak to moderate CutC inhibitory profiles of the choline analogs limit their further advancement into clinical translation. In this study, we introduce a glycomimetic-based approach for the identification of CutC inhibitors with intestinal metabolic stability. Our workflow started with screening of a small library of glycomimetics for metabolic stability in the presence of human intestinal S9 fraction. Further screening using an
Identifiants
pubmed: 34095847
doi: 10.1039/d0md00218f
pii: d0md00218f
pmc: PMC8126876
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1402-1412Informations de copyright
This journal is © The Royal Society of Chemistry.
Déclaration de conflit d'intérêts
There are no conflicts to declare.
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