Glycyrrhizic acid derivatives as Dengue virus inhibitors

• Published in: Bioorganic & medicinal chemistry letters 2019-10, Vol.29 (20), p.126645-126645, Article 126645
• Main Authors: Baltina, Lidia A., Tasi, Yan-Ting, Huang, Su-Hua, Lai, Hsueh-Chou, Baltina, Lia A., Petrova, Svetlana F., Yunusov, Marat S., Lin, Cheng-Wen
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Antiviral activity; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Cell Survival - drug effects; Chlorocebus aethiops; Cytopathogenic Effect, Viral - drug effects; Dengue - drug therapy; Dengue virus; Dengue Virus - drug effects; Derivatives; Glycyrrhizic acid; Glycyrrhizic Acid - analogs & derivatives; Glycyrrhizic Acid - chemistry; Glycyrrhizic Acid - pharmacology; Humans; Molecular Structure; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; Structure-Activity Relationship; Vero Cells - drug effects; Virus Replication - drug effects
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2019.126645

[Display omitted] •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.