Hepatitis C virus (HCV) is considered one of the most dangerous pathogens since about 3% of the world population is HCV-infectecl and the virus is a major cause of hepatitis, cirrhosis, and liver carcinoma. A need for a more efficient therapy prompted Lis to investigate new class of compounds, Such as tropolone derivatives that possess antiviral, antibacterial, and antifungal activities. To synthesize bromo-and morpholinomethyl-analogues of tropolone, the previously reported methods were modified. The influence of new derivatives on the activity of the helicase and NTP-ase of HCV was investigated. The most potent inhibitory effect in the fluorometric helicase assay was exerted by 3,7-dibromo-5-morpholinomethyltropolone, for which the IC50 value was at low micromolar range. All the morpholino-derivatives had inhibitory activities higher than those of the non-modified analogues. Low toxicity in a yeast-based toxicity assay indicates that these compounds could be further modified to develop potent inhibitors of the HCV helicase and of viral replication. (c) 2006 Elsevier Inc. All rights reserved.