Design, synthesis, and biological evaluation of crenatoside analogues as novel influenza neuraminidase inhibitors

• The synthesis of isocrenatoside analogues as novel NA inhibitors was accomplished.
• The new compounds were fully characterized by NMR and ESI-MS spectroscopy.
• Some compounds exhibited moderate activities and compound 2 h was the best with IC50 = 27.77 μg/ml against NAs.
• The structure-activity relationships of new isocrenatoside analogues was discussed.

Natural products, especially derived from TCMH, have been found to exert antiviral effects against influenza virus. Crenatoside, a phenylethanoid glycoside from Pogostemon cablin Benth, which has been shown as a novel effective NA inhibitor previously, is considered as the leading compound for our further SARs studies. This work presented design, synthesis of novel crenatoside analogues from readily available d-Glucose and l-rhamnose in a convergent manner. Furthermore, their biological activities and SARs were also investigated. Especially, compound 2 h showed impressive IC50 = 27.77 μg/mL against NAs, which is 3 folds more potent than the leading compound crenatoside (IC50 = 89.81 μg/mL). These results would promise their therapeutic potential for influenza disease.

Figure optionsDownload as PowerPoint slide