3-O-β-chacotriosyl benzyl ursolate inhibits entry of H5N1 influenza virus into target cells / 南方医科大学学报

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS AND CONCLUSION</b>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.</p>

Inhibitory activities of 3-O-β-chacotriosyl pentacyclic triterpenoids against the entry of H5 N1 influenza viruses in vitro / 中国药理学通报

Aim To study the inhibitory activities of potential new anti-influenza virus agents,3-O-β-chaco-triosyl pentacyclic triterpenoids against the entry of H5N1influenza viruses.Methods Three target com-pounds were designed and synthesized structurally re-lated to the lead compound 3-O-β-chacotriosyl dioscin derivative (1 )with inhibitory activities against H5N1 influenza viruses.The inhibitory activities of these tar-get compounds were tested at a cellular level pseudo vi-rus system targeting H5N1 influenza viruse entry.Re-sults All the compounds 1 a,1 b and 1 c showed po-tent inhibitory activities against the entry of A/Thai-land/Kan353/2004 pseudo virus into the target cells, of which compound 1 b showed the best inhibitory activ-ity with an IC50 value of (1.25 ±0.22)μmol·L-1. Conclusion The SARs analysis of these compounds indicated that replacement of the aglycone moiety of compound 1 with pentacyclic triterpenoids could in-crease antiviral activity.Different types of pentacyclic triterpen as aglycone residue had the significant influ-ence on the inhibitory activity (1 b >1 c >1 a),sug-gesting ursane type of triterpenes was superior to the two other kinds of triterpenes as aglycone residue.