Studies on the anti-hepatitis C virus activity of newly synthesized tropolone derivatives: Identification of NS3 helicase inhibitors that specifically inhibit subgenomic HCV replication

Abstract We synthesized new tropolone derivatives substituted with cyclic amines: piperidine, piperazine or pyrrolidine. The most active anti-helicase compound (IC 50  = 3.4 μM), 3,5,7-tri[(4′-methylpiperazin-1′-yl)methyl]tropolone ( 2 ), inhibited RNA replication by 50% at 46.9 μM (EC 50 ) and exhibited the lowest cytotoxicity (CC 50 ) >1 mM resulting in a selectivity index (SI = CC 50 /EC 50 ) >21. The most efficient replication inhibitor, 3,5,7-tri[(4′-methylpiperidin-1′-yl)methyl]tropolone ( 6 ), inhibited RNA replication with an EC 50 of 32.0 μM and a SI value of 17.4, whereas 3,5,7-tri[(3′-methylpiperidin-1′-yl)methyl]tropolone ( 7 ) exhibited a slightly lower activity with an EC 50 of 35.6 μM and a SI of 9.8.