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.

Carullo, G., Perri, M., Manetti, F., Aiello, F., Cristina Caroleo, M., Cione, E. (2019). Quercetin-3-Oleoyl Derivatives as New GPR40 Agonists: Molecular Docking Studies and Functional Evaluation. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 29(14), 1761-1764 [10.1016/j.bmcl.2019.05.018].

Quercetin-3-Oleoyl Derivatives as New GPR40 Agonists: Molecular Docking Studies and Functional Evaluation

Carullo, Gabriele
Investigation
;
Manetti, Fabrizio
Conceptualization
;
2019-01-01

Abstract

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.
2019
Carullo, G., Perri, M., Manetti, F., Aiello, F., Cristina Caroleo, M., Cione, E. (2019). Quercetin-3-Oleoyl Derivatives as New GPR40 Agonists: Molecular Docking Studies and Functional Evaluation. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 29(14), 1761-1764 [10.1016/j.bmcl.2019.05.018].
File in questo prodotto:
File Dimensione Formato  
2019_BiorgMedChemLett_GPR40_AV2.pdf

non disponibili

Tipologia: Post-print
Licenza: PUBBLICO - Pubblico con Copyright
Dimensione 566.69 kB
Formato Adobe PDF
566.69 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Quercetin-3-Oleoyl Derivatives.pdf

non disponibili

Tipologia: PDF editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 1.65 MB
Formato Adobe PDF
1.65 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1073149