Searching for a new anti-HCV therapy: Synthesis and properties of tropolone derivatives
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- 作者：Anna M. Boguszewska-Chachulska ; Mariusz Krawczyk ; Andż ; elika Najda ; Katarzyna Kopań ; ska ; Anna Stankiewicz-Drogoń ; Wł ; odzimierz Zagó ; rski-Ostoja and Maria Bretner
- 关键词：Hepatitis C virus ; Tropolone derivatives ; NS3 helicase ; Fluorometric assay
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2006
- 出版时间：10 March 2006
- 年：2006
- 卷：341
- 期：2
- 页码：641-647
- 全文大小：200 K
文摘
Hepatitis C virus (HCV) is considered one of the most dangerous pathogens since about 3 % of the world population is HCV-infected and the virus is a major cause of hepatitis, cirrhosis, and liver carcinoma. A need for a more efficient therapy prompted us 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.