title: Design, synthesis, and biological evaluation of antiviral agents targeting flavivirus envelope proteins.
abstract: Flavivirus envelope proteins (E proteins) have been shown to play a pivotal role in virus assembly, morphogenesis, and infection of host cells. Inhibition of flavivirus infection of a host cell by means of a small molecule envelope protein antagonist is an attractive strategy for the development of antiviral agents. Virtual screening of the NCI chemical database using the dengue virus envelope protein structure revealed several hypothetical hit compounds. Bioassay results identified a class of thiazole compounds with antiviral potency in cell-based assays. Modification of these lead compounds led to a series of analogues with improved antiviral activity and decreased cytotoxicity. The most active compounds 11 and 36 were effective in the low micromolar concentration range in a cellular assay system.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences and the PurdueCancer Center, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Ze
authors.initials: Z
authors.lastname: Li
authors.forename: Mansoora
authors.initials: M
authors.lastname: Khaliq
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Carol Beth
authors.initials: CB
authors.lastname: Post
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kuhn
authors.forename: Mark
authors.initials: M
authors.lastname: Cushman
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D005416:Flavivirus / Q000187:drug effects* / Q000378:metabolism*; D015686:Gene Products, env / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D015686:Gene Products, env