Design, Synthesis and Anti-influenza A Virus Evaluation of Oleanolic Acid C3-Glycoconjugates

Inhibitors targeting the entry stage of influenza viruses are a hot spot in the development of anti-influenza drugs. Our previous studies showed that oleanolic acid (OA) C28 glycoconjugates displayed strong anti-influenza virus activity. In this paper, a series of oleanolic acid C3 glycoconjugates 7a similar to 14c were designed and synthesized via copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The anti-influenza activities of all these compounds were evaluated in vitro. Among them, oleanane-12-enyl-28-benzyloxycarbonyl-3-O-(4-methylene-1,2,3-triazole-1-(2,3,4,6-tetra-O-acetyl-beta-D-galacto-side)) (12a) showed the strongest activity with an IC50 of 12.45 mu mol.L-1, and no obvious cytotoxic effect on MDCK cells was observed at 100 mu mol.L-1. Hemagglutination inhibition and molecular docking experiments indicated that compound 12a might target viral envelope hemagglutinin (HA), thus inhibiting the attachment of viruses to host cells. This study improved the structure-activity relationships of oleanolic acid and its derivatives against influenza virus, and provided a basis for further research on anti-virus by these natural products.

Automated summary

Inhibitors targeting the entry stage of influenza viruses are a key focus in anti-influenza drug development. A series of oleanolic acid C3 glycoconjugates were designed and synthesized, with compound 12a demonstrating the strongest anti-influenza activity. The compound may target viral envelope hemagglutinin (HA) to inhibit virus attachment to host cells, without showing cytotoxic effects on MDCK cells.