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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide