title: Analogs design, synthesis and biological evaluation of peptidomimetics with potential anti-HCV activity.
abstract: Two series of peptidomimetics were designed, prepared and evaluated for their anti-HCV activity. One series possesses a C-terminal carboxylate functionality. In the other series, the electrophilic vinyl sulfonate moiety was introduced as a novel class of HCV NS3/4A protease inhibitors. In vitro based studies were then performed to evaluate the efficacies of the inhibitors using Human hepatoma cells, with the vinyl sulfonate ester (10) in particular, found to have highly potent anti-HCV activity with an EC(50) = 0.296 μM. Finally, molecular modeling studies were performed through docking of the synthesized compounds in the HCV NS3/4A protease active site to assess their binding modes with the enzyme and gain further insight into their structure-activity relationships.
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
authors.forename: Deena S
authors.initials: DS
authors.lastname: Lasheen
authors.forename: Mohamed A H
authors.initials: MA
authors.lastname: Ismail
authors.forename: Dalal A
authors.initials: DA
authors.lastname: Abou El Ella
authors.forename: Nasser S M
authors.initials: NS
authors.lastname: Ismail
authors.forename: Sameh
authors.initials: S
authors.lastname: Eid
authors.forename: Susan
authors.initials: S
authors.lastname: Vleck
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Glenn
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Watts
authors.forename: Khaled A M
authors.initials: KA
authors.lastname: Abouzid
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D057786:Peptidomimetics; D015842:Serine Proteinase Inhibitors