Glycyrrhizic acid derivatives as Dengue virus inhibitors
| Autor: | Lidia A. Baltina, M. S. Yunusov, S. F. Petrova, Su Hua Huang, Lia A. Baltina, Yan Ting Tasi, Cheng Wen Lin, Hsueh Chou Lai |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cell Survival
viruses Clinical Biochemistry Anti-Inflammatory Agents Pharmaceutical Science Dengue virus medicine.disease_cause Virus Replication 01 natural sciences Biochemistry Antiviral Agents Article Dengue Small Molecule Libraries Structure-Activity Relationship Cytopathogenic Effect Viral Drug Discovery Chlorocebus aethiops medicine Animals Humans Antiviral activity Cytotoxicity Molecular Biology IC50 Vero Cells Cytopathic effect ComputingMethodologies_COMPUTERGRAPHICS Infectivity chemistry.chemical_classification Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry Dengue Virus Glycyrrhizic Acid Virology 0104 chemical sciences Amino acid 010404 medicinal & biomolecular chemistry Vero cell Molecular Medicine Isoleucine Derivatives |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters |
| ISSN: | 1464-3405 |
| Popis: | Graphical abstract Highlights • It is the first report to display structure-anti-DENV activity relationships of Glycyrrhizic acid (GL) derivatives. • GL conjugates with isoleucine 13 and 11-aminoundecanoic acid 17 have been identified as potent DENV2 inhibitors. • GL derivatives 13 and 17 showed lower IC50 values (1.2–1.3 μM) against DENV2 infectivity in Vero E6 cells than GL (IC50 8.1 μM). Dengue virus (DENV) is one of the most geographically distributed pathogenic flaviviruses transmitted by mosquitoes Aedes sps. In this study, the structure-antiviral activity relationships of Glycyrrhizic acid (GL) derivatives was evaluated by the inhibitory assays on the cytopathic effect (CPE) and viral infectivity of DENV type 2 (DENV2) in Vero E6 cells. GL (96% purity) had a low cytotoxicity to Vero E6 cells, inhibited DENV2-induced CPE, and reduced the DENV-2 infectivity with the IC50 of 8.1 μM. Conjugation of GL with amino acids or their methyl esters and the introduction of aromatic acylhydrazide residues into the carbohydrate part strongly influenced on the antiviral activity. Among compounds tested GL conjugates with isoleucine 13 and 11-aminoundecanoic acid 17 were found as potent anti-DENV2 inhibitors (IC50 1.2–1.3 μM). Therefore, modification of GL is a perspective way in the search of new antivirals against DENV2 infection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect