Design, synthesis, and biological evaluation of antiviral agents targeting flavivirus envelope proteins
| Autor: | Carol Beth Post, Ze Li, Richard J. Kuhn, Zhigang Zhou, Mansoora Khaliq, Mark Cushman |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Dengue virus medicine.disease_cause Antiviral Agents Virus Article Structure-Activity Relationship Protein structure Drug Discovery medicine Structure–activity relationship Cytotoxicity Binding Sites biology Molecular Structure Chemistry Flavivirus Gene Products env Biological activity biology.organism_classification Small molecule Virology Biochemistry Drug Design Molecular Medicine |
| Zdroj: | Journal of medicinal chemistry. 51(15) |
| ISSN: | 1520-4804 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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