title: Coumarins hinged directly on benzimidazoles and their ribofuranosides to inhibit hepatitis C virus.
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.
authors.affiliation: Department of Chemistry, National Central University, Jhongli 32001, Taiwan. tsay.susan@gmail.com
authors.forename: Shwu-Chen
authors.initials: SC
authors.lastname: Tsay
authors.forename: Jih Ru
authors.initials: JR
authors.lastname: Hwu
authors.forename: Raghunath
authors.initials: R
authors.lastname: Singha
authors.forename: Wen-Chieh
authors.initials: WC
authors.lastname: Huang
authors.forename: Yung Hsiung
authors.initials: YH
authors.lastname: Chang
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Hsu
authors.forename: Fa-Kuen
authors.initials: FK
authors.lastname: Shieh
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Lin
authors.forename: Kuo Chu
authors.initials: KC
authors.lastname: Hwang
authors.forename: Jia-Cherng
authors.initials: JC
authors.lastname: Horng
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Inge
authors.initials: I
authors.lastname: Vliegen
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000737:chemistry; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects; D006801:Humans; D013058:Mass Spectrometry; D008956:Models, Chemical; D015394:Molecular Structure; D010429:Pentoses / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D003374:Coumarins; D005663:Furans; D006027:Glycosides; D010429:Pentoses; C039281:furan