# 6-Chlorocoumarin Conjugates with Nucleobases and Nucleosides as Potent Anti-Hepatitis C Virus Agents

## TL;DR

Scientists created new compounds by linking 6-chlorocoumarin to nucleobases and nucleosides, which effectively inhibit hepatitis C virus replication in cells.

## Contribution

The study introduces novel 6-chlorocoumarin conjugates with nucleobases and nucleosides as potent anti-HCV agents.

## Key findings

- Three compounds showed strong inhibition of HCV replicon replication with EC50 values between 6.6 and 9.4 μM.
- The compounds exhibited selectivity indexes ranging from 16 to 41.
- Structure–activity relationships revealed the importance of coumarin attachment positions on purines and pyrimidines.

## Abstract

On the basis of a “chemo-combination strategy”, (6-chloro)coumarin was incorporated to purines and pyrimidines, as well as their corresponding nucleosides, with a –SCH2– linker at different positions under alkaline conditions. These conjugates were found to exert an antiviral effect on the 1b subgenomic replicon replication of the hepatitis C virus (HCV) in Huh 5-2 and Huh 9-13 cells. In this compound library containing 14 new compounds, 6-[(6′-chlorocoumarin-3′-yl)methylthio]purine, 6-(6′-chlorocoumarin-3′-yl)methylthio-9-(β-D-ribofuranos-1″-yl)purine, and 2-[(6′-chlorocoumarin-3′-yl)methylthio]uracil showed great inhibitory abilities, with EC50 values between 6.6 and 9.4 μM and selectivity indexes >16–41. Moreover, the structure–activity relationship between purines and pyrimidines is elucidated, which reveals the critical factor of the attachment of the coumarin moiety at different positions in purines and pyrimidines.