6-Chlorocoumarin Conjugates with Nucleobases and Nucleosides as Potent Anti-Hepatitis C Virus Agents
2025
Shu-Yu Lin | Wen-Chieh Huang | Shwu-Chen Tsay | Johan Neyts | Pieter Leyssen | Chun-Cheng Lin | Kuo Chu Hwang | Jia-Cherng Horng | Jih Ru Hwu
On the basis of a &ldquo:chemo-combination strategy&rdquo:, (6-chloro)coumarin was incorporated to purines and pyrimidines, as well as their corresponding nucleosides, with a &ndash:SCH2&ndash: 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&prime:-chlorocoumarin-3&prime:-yl)methylthio]purine, 6-(6&prime:-chlorocoumarin-3&prime:-yl)methylthio-9-(&beta:-D-ribofuranos-1&Prime:-yl)purine, and 2-[(6&prime:-chlorocoumarin-3&prime:-yl)methylthio]uracil showed great inhibitory abilities, with EC50 values between 6.6 and 9.4 &mu:M and selectivity indexes >:16&ndash:41. Moreover, the structure&ndash: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.
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