Synthesis of new benzimidazole–coumarin conjugates as anti-hepatitis C virus agents

Nineteen new conjugated compounds were successfully synthesized by a one-flask method from benzimidazole and coumarin derivatives. A methylenethio linker was used to connect these two kinds of derivatives. In addition, substituted benzimidazol-2-thiones were also coupled with β- d-glucose peracetate...

Full description

Saved in:
Bibliographic Details
Published in:Antiviral research 2008-02, Vol.77 (2), p.157-162
Main Authors: Hwu, Jih Ru, Singha, Raghunath, Hong, Shih Ching, Chang, Yung Hsiung, Das, Asish R., Vliegen, Inge, De Clercq, Erik, Neyts, Johan
Format: Article
Language:English
Subjects:
Animals
Anti-HCV
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Antiviral Agents - chemical synthesis
Antiviral Agents - pharmacology
Benzimidazole
Benzimidazoles - chemical synthesis
Benzimidazoles - chemistry
Benzimidazoles - pharmacology
Biological and medical sciences
Cell Line
Conjugate
Coumarin
Coumarins - chemical synthesis
Coumarins - chemistry
Coumarins - pharmacology
Dose-Response Relationship, Drug
Genome, Viral
Hepacivirus - drug effects
Hepacivirus - growth & development
Hepatitis C virus
Humans
Medical sciences
Molecular Structure
N-Glucosides
Pharmacology. Drug treatments
RNA, Viral - genetics
Structure-Activity Relationship
Viruses - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Nineteen new conjugated compounds were successfully synthesized by a one-flask method from benzimidazole and coumarin derivatives. A methylenethio linker was used to connect these two kinds of derivatives. In addition, substituted benzimidazol-2-thiones were also coupled with β- d-glucose peracetate; the resultant glucosides were further converted to the corresponding 2-(methylthio)coumarin derivatives. Their activity against the hepatitis C virus was tested; two of the most potent compounds 2-[(6′-bromocoumarin-3′-yl)methylenethio]-5-fluorobenzimidazole ( 4i) and its derivative 1-[(2″,3″,4″,6″-tetra- O-acetyl)glucopyranos-1″-yl]-2-[(6′-bromocoumarin-3′-yl)methylenethio]benzimidazole ( 7c) showed EC 50 values of 3.4 μM and 4.1 μM, respectively. At a concentration of 5.0 μM, compound 7c inhibited HCV RNA replication by 90% and had no effect on cell proliferation. Given these data, a structure–activity relationship was established.
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2007.09.003