Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Exploring new scaffolds for angiotensin II receptor antagonism
Δημιουργός/Συγγραφέας:	Kritsi E. Matsoukas M.-T. Potamitis C. Karageorgos V. Detsi A. Magafa V. Liapakis G. [EL] Μαυρομούστακος, Θωμάς[EN] Mavromoustakos, Thomas [EL] Ζουμπουλάκης, Παναγιώτης[EN] Zoumpoulakis, Panagiotis
Εκδότης:	Elsevier Ltd
Ημερομηνία:	2016
Γλώσσα:	Αγγλικά
ISSN:	0968-0896
DOI:	10.1016/j.bmc.2016.07.047
Άλλο:	PubMed ID: 27480029
Περίληψη:	Nowadays, AT1receptor (AT1R) antagonists (ARBs) constitute the one of the most prevalent classes of antihypertensive drugs that modulate the renin-angiotensin system (RAS). Their main uses include also treatment of diabetic nephropathy (kidney damage due to diabetes) and congestive heart failure. Towards this direction, our study has been focused on the discovery of novel agents bearing different scaffolds which may evolve as a new class of AT1receptor antagonists. To fulfill this aim, a combination of computational approaches and biological assays were implemented. Particularly, a pharmacophore model was established and served as a 3D search query to screen the ChEMBL15 database. The reliability and accuracy of virtual screening results were improved by using molecular docking studies. In total, 4 compounds with completely diverse chemical scaffolds from potential ARBs, were picked and tested for their binding affinity to AT1receptor. Results revealed high nanomolar to micromolar affinity (IC50) for all the compounds. Especially, compound 4 exhibited a binding affinity of 199 nM. Molecular dynamics simulations were utilized in an effort to provide a molecular basis of their binding to AT1R in accordance to their biological activities.
Τίτλος πηγής δημοσίευσης:	Bioorganic and Medicinal Chemistry
Τόμος/Κεφάλαιο:	24
Τεύχος:	18
Σελίδες:	4444-4451
Θεματική Κατηγορία:	[EL] Βιοχημεία[EN] Biochemistry
Λέξεις-Κλειδιά:	Angiotensin II receptor antagonists Molecular Dynamics simulations Pharmacological characterization Pharmacophore modeling Virtual screening
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2016 Elsevier Ltd
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο