Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Design and synthesis of nitrate esters of aromatic heterocyclic compounds as pharmacological preconditioning agents
Δημιουργός/Συγγραφέας:	Fotopoulou, Theano Iliodromitis, Efstathios K. [EL] Κουφάκη, Μαρία[EN] Koufaki, Maria Tsotinis, Andrew Zoga, Anastasia Gizas, Vassilis Pyriochou, Anastasia Papapetropoulos, Andreas Andreadou, Ioanna Kremastinos, Dimitrios Th
Εκδότης:	Pergamon
Τόπος έκδοσης:	OXFORD
Ημερομηνία:	2008-04-15
Γλώσσα:	Αγγλικά
ISSN:	0968-0896
DOI:	10.1016/j.bmc.2008.02.051
Περίληψη:	Ischemic preconditioning (IPC) constitutes an endogenous protective mechanism in which one or more brief periods of myocardial ischemia and reperfusion render the myocardium resistant to a subsequent more-sustained ischemic insult. Pharmacological preconditioning represents an ideal alternative of IPC. We now describe the design and synthesis of indole, quinoline, and purine systems with an attached pharmacophoric nitrate ester group. The indole and quinoline derivatives 4 and 5 possess structural features of the nitrate containing K-ATP channel openers. Purine analogues 11 and 12, substituted at the position 6 by a piperidine moiety and at position 9 by an alkyl nitrate, could combine the effects of the nitrate containing KATP channel openers and those of adenosine. Compound 13 bears the nicotinamide moiety of nicorandil instead of nitrate ester. Compounds 4, 5, and 11 reduced infarction and the levels of malondialdehyde (MDA) at reperfusion in anesthetized rabbits. Compounds 12 and 13 did not significantly reduce the infarct size. Analogues 4 and 5 increased cGMP and MDA during ischemia, while combined analogue 4 and mitoKATP blocker 5-hydroxydecanoic acid (5-HD) abrogated this benefit suggesting an action through mitoKATP channel opening. Treatment with derivative 11 combined with 5-HD as well as treatment with 11 and adenosine receptor blocker 8-(p-sulfophenyl) theophylline (SPT) did not abrogate cardioprotection. Compound 11 is a lead molecule for the synthesis of novel analogues possessing a dual mode of action through cGMP-mitoKATP channel opening-free radicals and through adenosine receptors.
Τίτλος πηγής δημοσίευσης:	Bioorganic & Medicinal Chemistry
Τόμος/Κεφάλαιο:	16
Τεύχος:	8
Σελίδες:	4523-4531
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General) [EL] Χημεία (Γενικά)[EN] Chemistry (General) [EL] Οργανική χημεία[EN] Organic chemistry [EL] Φαρμακευτική[EN] Pharmacy and materia medica
Λέξεις-Κλειδιά:	pharmacological preconditioning K-ATP channel openers adenosine infarct size Chemistry, Medicinal
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2008 Elsevier Ltd. All rights reserved.
Ηλεκτρονική διεύθυνση περιοδικού (link) :	http://www.elsevier.com/locate/bmc
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Οργανικής και Φαρμακευτικής Χημείας (ΙΟΦΧ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο