Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Synthesis, kinetic and conformational studies of 2-substituted-5-(β-d-glucopyranosyl)-pyrimidin-4-ones as potential inhibitors of glycogen phosphorylase
Δημιουργός/Συγγραφέας:	Mavreas, Konstantinos F Neofytos, Dionysios D [EL] Χρυσίνα, Ευαγγελία Δ.[EN] Chrysina, Evangelia D. Venturini, Alessandro Gimisis, Thanasis
Ημερομηνία:	2020-11-22
Γλώσσα:	Αγγλικά
ISSN:	1420-3049
DOI:	10.3390/molecules25225463
Άλλο:	33266408
Περίληψη:	Dysregulation of glycogen phosphorylase, an enzyme involved in glucose homeostasis, may lead to a number of pathological states such as type 2 diabetes and cancer, making it an important molecular target for the development of new forms of pharmaceutical intervention. Based on our previous work on the design and synthesis of 4-arylamino-1-(β-d-glucopyranosyl)pyrimidin-2-ones, which inhibit the activity of glycogen phosphorylase by binding at its catalytic site, we report herein a general synthesis of 2-substituted-5-(β-d-glucopyranosyl)pyrimidin-4-ones, a related class of metabolically stable, C-glucosyl-based, analogues. The synthetic development consists of a metallated heterocycle, produced from 5-bromo-2-methylthiouracil, in addition to protected d-gluconolactone, followed by organosilane reduction. The methylthio handle allowed derivatization through hydrolysis, ammonolysis and arylamine substitution, and the new compounds were found to be potent (μM) inhibitors of rabbit muscle glycogen phosphorylase. The results were interpreted with the help of density functional theory calculations and conformational analysis and were compared with previous findings.
Τίτλος πηγής δημοσίευσης:	Molecules (Basel, Switzerland)
Τόμος/Κεφάλαιο:	25
Τεύχος:	22
Σελίδες:	5463
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General) [EL] Βιοτεχνολογία[EN] Biotechnology [EL] Χημική Βιολογία[EN] Chemical Biology [EL] Δομική Βιολογία[EN] Structural Biology
Λέξεις-Κλειδιά:	5-(β-d-glucopyranosyl)pyrimidin-4-one synthesis DFT conformational analysis Cancer Catalytic site inhibitors Glycogen phosphorylase Type 2 diabetes Animals Catalytic Domain Computational Biology Drug Design Enzyme Inhibitors Glucose Glycogen Phosphorylase, Muscle Form Kinetics Molecular Conformation Molecular Docking Simulation Muscle, Skeletal Pyrimidinones Rabbits
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.mdpi.com/1420-3049/25/22/5463
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://www.mdpi.com/journal/molecules
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο