Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus

Abstract

A series of new conjugated compounds with a -SCH 2 -linkage were synthesized by chemical methods from imidazole and coumarin derivatives. The experimental results indicate that of the twenty newly synthesized imidazole-coumarin conjugates, three of them exhibited appealing EC 50 values (5.1-8.4 µM) and selective indices >20 against hepatitis C virus. Their potency and selectivity were increased substantially by modification of their structure with two factors: imidazole nucleus with a hydrogen atom at the N(1) position and coumarin nucleus with a substituent, such as Cl, F, Br, Me, and OMe. These guidelines provide valuable information for further development of conjugated compounds as anti-viral agents.

An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities

“…As already mentioned, coumarins have been studied also for their potential application as anti-hepatitis agents. Tsay and co-workers studied the activity against hepatitis C virus (HCV) of some unnatural imidazole-coumarin conjugates [ 130 ]. Above all, three compounds ( 90 – 92 , Figure 33 ) showed a noteworthy antiviral activity against HCV with EC 50 values ranging from 5.1 to 8.4 μM and selective indices (SI = CC 50 /EC 50 , which is a measure for the therapeutic window of the compound in an assay system) higher than 20.…”

Design, Synthesis and Antifungal Activity of Coumarin Ring-Opening Derivatives

“…As the structural core, coumarin occurs widely in natural products, drugs and agrochemicals (Figure 1), these important applications have generated considerable interest in this ring system and various fused coumarin derivatives have been reported [3][4][5][6]: Osthole, a natural O-methylated coumarin found in Cnidium Monnieri, a traditional Chinese herbal medicine that has been used as as a fungicidein China for a long history,and shows antifungal activity against Rhizoctonia solani and a broad spectrum of other phytopathogenic fungi [7][8][9]; Warfarin and Acenocoumarol are anticoagulants normally used in the prevention of thrombosis and thromboembolism, function as the vitamin K antagonists [10][11][12]; and Coumoxystrobin (SYP-3375) is a coumarin-containing strobilurin fungicide that contains an (E)-methyl 3-methoxy-2-phenylacrylate substructure and displays a broad spectrum of antifungal activity [13][14][15]. In our previous work, Osthole was used as the lead structure to carry out structural optimization, and some synthesized furan [3,2-c]coumarin derivatives showed potent antifungal activity [16][17][18].…”

Synthesis and Applications of 2‐Substituted Imidazole and Its Derivatives: A Review

“…Compound 85 , aqueous ammonium hydroxide, and 3‐(chloromethyl)coumarin 86 were stirred at room temperature to afford final product 1‐( β ‐ d ‐ribofuranos‐1″‐yl)‐2‐[(coumarin‐3′‐yl)methylthio]imidazole 87 (Scheme ). These compounds were identified as good activity against the hepatitis C virus .…”