In this study three new classes of linear <i>N</i>-tricyclic compounds, derived by condensation of the quinoline nucleus with 1,2,3-triazole, imidazole or pyrazine, were synthesized, obtaining triazolo[4,5-<i>g</i>]quinolines, imidazo[4,5-<i>g</i>]quinolines and pyrido[2,3-<i>g</i>]quinoxalines, respectively. Title compounds were tested in cell-based assays for cytotoxicity and antiviral activity against RNA viruses representative of the three genera of the <i>Flaviviridae</i> family, that is BVDV (<i>Pestivirus</i>), YFV (<i>Flavivirus</i>) and HCV (<i>Hepacivirus</i>). Quinoline derivatives were also tested against representatives of other RNA virus families containing single-stranded, either positive-sense (ssRNA<sup>+</sup>) or negative-sense (RNA<sup>−</sup>), and double-stranded genomes (dsRNA), as well as against representatives of two DNA virus families. Some quinolines showed moderate, although selective activity against CVB-5, Reo-1 and RSV. However, derivatives belonging to all classes showed activity against BVDV. Among the most potent were the bis-triazoloquinoline <b>1m</b>, the imidazoquinolines <b>2e</b> and <b>2h</b>, and the pyridoquinoxalines <b>4h</b>, <b>4j</b> and <b>5n</b> (EC<sub>50</sub> range 1–5 μM). When tested in a replicon assay, compound <b>2h</b> was the sole derivative to also display anti-HCV activity (EC<sub>50</sub> = 3.1 μM). In enzyme assays, <b>1m</b>, <b>2h</b>, <b>5m</b> and <b>5n</b> proved to be potent inhibitors of the BVDV RNA-dependent RNA polymerase (RdRp), while only <b>2h</b> also inhibited the recombinant HCV enzyme
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