title: Aryl-substituted aminobenzimidazoles targeting the hepatitis C virus internal ribosome entry site.
abstract: We describe the exploration of N1-aryl-substituted benzimidazoles as ligands for the hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA. The design of the compounds was guided by the co-crystal structure of a benzimidazole viral translation inhibitor in complex with the RNA target. Structure-binding activity relationships of aryl-substituted benzimidazole ligands were established that were consistent with the crystal structure of the translation inhibitor complex.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States.
authors.forename: Kejia
authors.initials: K
authors.lastname: Ding
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States.
authors.forename: Annie
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Boerneke
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Dibrov
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States. Electronic address: tch@ucsd.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermann
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D008024:Ligands; D012367:RNA, Viral
keywords: Antivirals; HCV; RNA targeting; Translation inhibitor