| Searching for a new anti-HCV therapy: synthesis and properties of tropolone derivatives. | |
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MedLine Citation:
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PMID: 16438939 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Anna M Boguszewska-Chachulska; Mariusz Krawczyk; Andzelika Najda; Katarzyna Kopańska; Anna Stankiewicz-Drogoń; Włodzimierz Zagórski-Ostoja; Maria Bretner |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-01-17 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 341 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2006 Mar |
Date Detail:
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Created Date: 2006-01-31 Completed Date: 2006-04-18 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 641-7 Citation Subset: IM |
Affiliation:
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Institute of Biochemistry and Biophysics PAS, Pawińskiego 5a, 02-106 Warsaw, Poland. annach@ibb.waw.pl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphatases
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chemistry Adenosine Triphosphate / metabolism Antiviral Agents / pharmacology* DNA / chemistry Dose-Response Relationship, Drug Fluorometry / methods Hepacivirus / metabolism* Hepatitis C / drug therapy* Humans Inhibitory Concentration 50 Magnetic Resonance Spectroscopy / methods Models, Chemical Spectrometry, Mass, Electrospray Ionization / methods Temperature Tropolone / analogs & derivatives*, chemical synthesis, pharmacology Viral Nonstructural Proteins / metabolism Virus Replication / drug effects |
| Chemical | |
Reg. No./Substance:
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0/3,7-dibromo-5-morpholinomethyltropolone; 0/Antiviral Agents; 0/NS3 protein, hepatitis C virus; 0/Viral Nonstructural Proteins; 533-75-5/Tropolone; 56-65-5/Adenosine Triphosphate; 9007-49-2/DNA; EC 3.6.1.-/Adenosine Triphosphatases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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