title: Synthesis, molecular modeling, and biological evaluation of novel benzimidazole derivatives as inhibitors of hepatitis C virus RNA replication.
abstract: In this study, synthesis and docking studies of a series of new benzimidazole derivatives linked to substituted pyrimidines either through the methylenethio linkage or its bioisosteric methylene amino bridge were carried out. All the synthesized compounds were evaluated for their hepatitis C virus (HCV) RNA replication-inhibitory activity. Compounds 4d, 4f, and 4h were found to be more potent than VX-950 (IC50/90 of 4d=0.123/0.321, 4f=0.145/0.345, 4h=0.129/0.432, VX-950=0.20/0.45 µM, respectively) and 6d (IC50/90=0.116/0.452 µM) displayed activity very similar to that of the standard. Compounds 4d, 4f, 4h, and 6d were potent HCV RNA replication inhibitors and are good drug candidates for further investigations.
authors.affiliation: Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries Research, National Research Center.
authors.forename: Hoda Ibrahim
authors.initials: HI
authors.lastname: El Diwani
authors.forename: Heba Tawfik
authors.initials: HT
authors.lastname: Abdel-Mohsen
authors.forename: Ismail
authors.initials: I
authors.lastname: Salama
authors.forename: Fatma Abdel-Fattah
authors.initials: FA
authors.lastname: Ragab
authors.forename: Mostafa Mahmoud
authors.initials: MM
authors.lastname: Ramla
authors.forename: Shadia Ahmed
authors.initials: SA
authors.lastname: Galal
authors.forename: Mohamed Mostafa
authors.initials: MM
authors.lastname: Abdalla
authors.forename: Abeer
authors.initials: A
authors.lastname: Abdel-Wahab
authors.forename: Maha Adel
authors.initials: MA
authors.lastname: El Demellawy
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D012367:RNA, Viral / Q000096:biosynthesis / Q000187:drug effects*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D012367:RNA, Viral