titoli, abstracts, parole chiave >>>
Sintesi e valutazione di sistemi azotati triciclici aromatici come possibili agenti antivirali

Briguglio, Irene (2011) Sintesi e valutazione di sistemi azotati triciclici aromatici come possibili agenti antivirali. Doctoral Thesis.

[img]
Preview
Full text disponibile come PDF Richiede visualizzatore di PDF come GSview, Xpdf o Adobe Acrobat Reader
4Mb

Abstract

In this PhD project three new classes of linear N-tricyclic compounds, derived by condensation of the quinoline nucleus with 1,2,3-triazole, imidazole or pyrazine, were synthesized, obtaining triazolo[4,5-g]quinolines, imidazo[4,5-g]quinolines and pyrido[2,3-g]quinoxalines, respectively. Title compounds were tested in cell-based assays for citotoxicity and antiviral activity against RNA viruses representative of the three genera of the Flaviviridae family: BVDV (Pestivirus), YFV (Flavivirus) and HCV (Hepacivirus). Quinoline derivatives were also tested against representatives of other RNA virus families containing single-stranded, either positive (ssRNA+) or negative (ssRNA-) sense, and double-stranded genomes (dsRNA), as well as against representatives of two DNA virus families. Derivatives belonging to all classes showed activity against BVDV. Among the most potent was the imidazoquinolines 1α (EC50=0.3 μM) and 1β (EC50=1.2 microM), the bis-triazoloquinoline 14 (EC50=1 μM), and the pyridoquinoxalines 25, 26 and 28 (EC50 range 2.6–5 μM). When tested in a replicon assay, only compounds 1α and 1β displayed a good anti-HCV activity, whereas derivative 1β resulted the most potent (EC50=3.1 μM). Furthermore, in enzyme assays, 1β, 14 and 25 proved to be potent inhibitors of the BVDV RNA-dependent RNA polymerase (RdRp), while only 1β also inhibited the recombinant HCV enzyme. Finally, some tested quinolines showed moderate, although selective activity against CVB-5, Reo-1 and RSV.

Item Type:Doctoral Thesis
ID Code:6752
Contributors:Carta, Antonio
Publisher:Università degli studi di Sassari
Uncontrolled Keywords:Triazolo[4,5-g]quinolines, imidazo[4,5-g]quinolines, pyrido[2,3-g]quinoxalines, HCV, BVDV
Subjects:Area 03 - Scienze chimiche > CHIM/08 Chimica farmaceutica
Divisions:001 Università di Sassari > 01 Dipartimenti > Farmaco, chimico, tossicologico
Cicli, scuole e corsi:Ciclo 24 > Scuole > Scienze e tecnologie chimiche > Scienze farmaceutiche
Deposited On:28 Mar 2012 11:46

I documenti depositati in UnissResearch sono protetti dalle leggi che regolano il diritto d'autore

Repository Staff Only: item control page