The influenza virus
infection remains a significant threat to public health and the increase of
antiviral resistance to available drugs generates an urgent need for new
antiviral compounds. Starting from the natural, antivirally active compound
glycyrrhizin, spacer-bridged derivatives were generated with improved
antiviral activity against the influenza A virus
infection. Simplified analogues of the
triterpene saponin glycyrrhizin containing 1-thio-β-D-glucuronic
acid residues have been prepared in good yields by alkylation of 3-amino and 3-thio derivatives of
glycyrrhetinic acid with a 2-iodoethyl 1-thio-β-D-glucopyranosiduronate derivative. The spacer-connected 3-amino derivatives were further transformed into N-acetylated and N-succinylated derivatives. The deprotected compounds containing these
carboxylic acid appendices mimic the glycon part of
glycyrrhizin as well as the hemisuccinate derivative of
glycyrrhetinic acid,
carbenoxolone.
Antiviral activities of the compounds were determined in a
biological test based on influenza A virus-infected cells, wherein the 3-(2-thioethyl)-N-acetylamino- and 3-(2-thioethyl)-thio-linked
glucuronide derivatives were effective inhibitors with IC(50) values as low as 54 µM.