A benzoxazole derivative as an inhibitor of anaerobic choline metabolism by human gut microbiota.

ABSTRACT: 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 wit

SUBMITTER: Gabr MT 

PROVIDER: S-EPMC8126876 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature