Glycyrrhizic acid derivatives as Dengue virus inhibitors

Lidia A Baltina; Yan-Ting Tasi; Su-Hua Huang; Hsueh-Chou Lai; Lia A Baltina; Svetlana F Petrova; Marat S Yunusov; Cheng-Wen Lin

doi:10.1016/j.bmcl.2019.126645

Glycyrrhizic acid derivatives as Dengue virus inhibitors

Bioorg Med Chem Lett. 2019 Oct 15;29(20):126645. doi: 10.1016/j.bmcl.2019.126645. Epub 2019 Aug 29.

Authors

Lidia A Baltina¹, Yan-Ting Tasi², Su-Hua Huang³, Hsueh-Chou Lai⁴, Lia A Baltina⁵, Svetlana F Petrova⁵, Marat S Yunusov⁵, Cheng-Wen Lin⁶

Affiliations

¹ Ufa Institute of Chemistry, Ufa Federal Research Centre of RAS, 71, Prospect Oktyabrya, Ufa 450054, Russian Federation. Electronic address: baltina@anrb.ru.
² Department of Medical Laboratory Science and Biotechnology, China Medical University, 91, Hsueh-Shih Rd., Taichung 40402, Taiwan, ROC; Department of Biotechnology, Asia University, 500, Lioufeng Rd., Wufeng, Taichung 41354, Taiwan, ROC.
³ Department of Biotechnology, Asia University, 500, Lioufeng Rd., Wufeng, Taichung 41354, Taiwan, ROC.
⁴ School of Chinese Medicine, China Medical University, 91, Hsueh-Shih Rd., Taichung 40402, Taiwan, ROC; Division of Hepato-gastroenterology, Department of Internal Medicine, China Medical University Hospital, 2, Yude Rd., Taichung 40447, Taiwan, ROC.
⁵ Ufa Institute of Chemistry, Ufa Federal Research Centre of RAS, 71, Prospect Oktyabrya, Ufa 450054, Russian Federation.
⁶ Department of Medical Laboratory Science and Biotechnology, China Medical University, 91, Hsueh-Shih Rd., Taichung 40402, Taiwan, ROC; Department of Biotechnology, Asia University, 500, Lioufeng Rd., Wufeng, Taichung 41354, Taiwan, ROC; Chinese Medicine Research Center, China Medical University, 91, Hsueh-Shih Rd., Taichung 40402, Taiwan, ROC. Electronic address: cwlin@mail.cmu.edu.tw.

Abstract

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.

Keywords: Antiviral activity; Dengue virus; Derivatives; Glycyrrhizic acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / chemistry*
Anti-Inflammatory Agents / pharmacology
Antiviral Agents / chemistry*
Antiviral Agents / pharmacology
Cell Survival / drug effects
Chlorocebus aethiops
Cytopathogenic Effect, Viral / drug effects
Dengue / drug therapy*
Dengue Virus / drug effects*
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

Substances

Anti-Inflammatory Agents
Antiviral Agents
Small Molecule Libraries
Glycyrrhizic Acid