Coumarins hinged directly on benzimidazoles and their ribofuranosides to inhibit hepatitis C virus

Shwu Chen Tsay, Jih Ru Hwu, Raghunath Singha, Wen Chieh Huang, Yung Hsiung Chang, Ming Hua Hsu, Fa Kuen Shieh, Chun Cheng Lin, Kuo Chu Hwang, Jia Cherng Horng, Erik De Clercq, Inge Vliegen, Johan Neyts

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Abstract

A new compound library that contained 20 hinged benzimidazole-coumarin hybrids and their β-d-ribofuranosides was established. The anti-hepatitis C virus (HCV) activity of all novel coumarin derivatives, which were obtained by use of organic synthetic methods, was tested. Two of these hybrids exhibited appealing EC50 values of as low as 3.0 and 5.5 μM. The best selectivity index was 14. The incorporation of a d-ribofuranose into the hinged hybrids provided the corresponding nucleosides with the β configuration, one of which inhibited HCV replication with an EC50 value of 20 μM. Additionally, the structure-activity relationship is elucidated on the basis of the functional groups that were attached to the nuclei of benzimidazole, coumarin, and ribofuranose of the hybrids.

Original languageEnglish
Pages (from-to)290-298
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume63
DOIs
Publication statusPublished - 2013 Mar 18

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Tsay, S. C., Hwu, J. R., Singha, R., Huang, W. C., Chang, Y. H., Hsu, M. H., Shieh, F. K., Lin, C. C., Hwang, K. C., Horng, J. C., De Clercq, E., Vliegen, I., & Neyts, J. (2013). Coumarins hinged directly on benzimidazoles and their ribofuranosides to inhibit hepatitis C virus. European Journal of Medicinal Chemistry, 63, 290-298. https://doi.org/10.1016/j.ejmech.2013.02.008