Abstract: Objective To study the inhibitory activities of 3-O-β-chacotriosyl benzyl ursolate and its derivatives as potential new
anti-influenza virus agents against the entry of H5N1 influenza viruses into the target cells. Methods Four target compounds
were designed and synthesized, which were structurally related to the lead compound 3-O-β-chacotriosyl methyl ursolate (1).
The inhibitory activities of these compounds were tested at a cellular level psuedovirus system targeting H5N1 influenza
viruse entry. Results and Conclusion The compounds 1b, 1c and 1d showed potent inhibitory activities against the entry
of A/Thailand/Kan353/2004 pseudovirus into the target cells, and among them compound 1d showed the strongest inhibitory
activity with an IC50 value of 0.96±0.10 μmol/L. The structure-activity relationship analysis of these compounds indicated that
when 17-COOH of ursolic acid was esterified, introduction of Me groups rather than aryl groups more strongly enhanced the
inhibitory activity. Changing 17-COOH of ursolic acid into amide could increase the antiviral activity and decrease the
cytotoxicity of the compounds in MDCK cells.