Quercetin-3-oleoyl derivatives as new GPR40 agonists: Molecular docking studies and functional evaluation.
GPR40 allosteric site
Insulin secretion
Oleic acid
Quercetin
Type 2 diabetes
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 07 2019
15 07 2019
Historique:
received:
15
02
2019
revised:
07
05
2019
accepted:
11
05
2019
pubmed:
21
5
2019
medline:
10
9
2020
entrez:
21
5
2019
Statut:
ppublish
Résumé
The G-protein-coupled receptor 40 (GPR40) is an attractive molecular target for the treatment of type 2 diabetes mellitus. Previously, based on the natural oleic acid substrate, an exogenous ligand for this receptor, named AV1, was synthesized. In this context, here we validated the activity of AV1 as a full agonist, while the corresponding catechol analogue, named AV2, was investigated for the first time. The ligand-protein interaction between this new molecule and the receptor was highlighted in the lower portion of the GPR40 groove that generally accommodates DC260126. The functional assays performed have demonstrated that AV2 is a suitable GPR40 partial agonist, showing a therapeutic potential and representing a useful tool in the management of type 2 diabetes.
Identifiants
pubmed: 31104992
pii: S0960-894X(19)30315-4
doi: 10.1016/j.bmcl.2019.05.018
pii:
doi:
Substances chimiques
Quercetin
9IKM0I5T1E
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1761-1764Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.