Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Glucose-derived spiro-isoxazolines are anti-hyperglycemic agents against type 2 diabetes through glycogen phosphorylase inhibition
Δημιουργός/Συγγραφέας:	Goyard D. Kónya B. Chajistamatiou A.S. [EL] Χρυσίνα, Ευαγγελία Δ.[EN] Chrysina, Evangelia D. Leroy J. Balzarin S. Tournier M. Tousch D. Petit P. Duret C. Maurel P. Somsák L. Docsa T. Gergely P. Praly J.-P. Azay-Milhau J. Vidal S.
Εκδότης:	Elsevier Masson SAS
Ημερομηνία:	2016
Γλώσσα:	Αγγλικά
ISSN:	0223-5234
DOI:	10.1016/j.ejmech.2015.12.004
Άλλο:	PubMed ID: 26708111
Περίληψη:	Glycogen phosphorylase (GP) is a target for the treatment of hyperglycaemia in the context of type 2 diabetes. This enzyme is responsible for the depolymerization of glycogen into glucose thereby affecting the levels of glucose in the blood stream. Twelve new d-glucopyranosylidene-spiro-isoxazolines have been prepared from O-peracylated exo-D-glucals by regio- and stereoselective 1,3-dipolar cycloaddition of nitrile oxides generated in situ by treatment of the corresponding oximes with bleach. This mild and direct procedure appeared to be applicable to a broad range of substrates. The corresponding O-unprotected spiro-isoxazolines were evaluated as glycogen phosphorylase (GP) inhibitors and exhibited IC50 values ranging from 1 to 800 μM. Selected inhibitors were further evaluated in vitro using rat and human hepatocytes and exhibited significant inhibitory properties in the primary cell culture. Interestingly, when tested with human hepatocytes, the tetra-O-acetylated spiro-isoxazoline bearing a 2-naphthyl residue showed a much lower IC50 value (2.5 μM), compared to that of the O-unprotected analog (19.95 μM). The most promising compounds were investigated in Zucker fa/fa rat model in acute and sub-chronic assays and decreased hepatic glucose production, which is known to be elevated in type 2 diabetes. This indicates that glucose-based spiro-isoxazolines can be considered as anti-hyperglycemic agents in the context of type 2 diabetes.
Τίτλος πηγής δημοσίευσης:	European Journal of Medicinal Chemistry
Τόμος/Κεφάλαιο:	108
Σελίδες:	444-454
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General) [EL] Χημεία (Γενικά)[EN] Chemistry (General)
Λέξεις-Κλειδιά:	Carbohydrates Glycogen phosphorylase inhibitors Hepatic glucose production Hepatocytes Spiro-isoxazolines Type 2 diabetes Zucker rats
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2015 Elsevier Masson SAS.
Σημειώσεις:	Seventh Framework Programme, FP7; European Commission, EC; Agence Nationale de la Recherche, ANR: ANR-08-BLAN-0305; Hungarian Scientific Research Fund, OTKA: OTKA 109450; Magyar Tudományos Akadémia, MTA: 4576; Centre National de la Recherche Scientifique, CNRS; European Social Fund, ESF; Université Claude Bernard Lyon 1, UCBL; Debreceni Egyetem, DE
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο