Synthesis and antiproliferative activity of helonioside A, 3′,4′,6′-tri-O-feruloylsucrose, lapathoside C and their analogs

The first total synthesis of natural phenylpropanoid sucrose esters (PSEs) helonioside A 1, 3′,4′,6′-tri-O-feruloylsucrose 2 and lapathoside C 3 along with 17 unnatural PSE analogs has been successfully accomplished in a short and simple synthetic route. A selected set of 17 synthesized PSEs were evaluated for the antiproliferative activity against human cervical epithelioid carcinoma (HeLa) cell lines using MTS assay method. Eleven (11) compounds showed significant antiproliferative activity with their IC50values ranging from 0.16 to 6.01 μM. The structure–activity-relationship studies revealed that the antiproliferative activity is influenced by the lipophilicity and number of feruloyl substituents on these compounds. The preliminary screening indicated that these compounds are potentially very valuable source for new lead chemotherapeutics.

Graphical abstractHelonioside A, 3′,4′,6′-tri-O-feruloylsucrose, lapathoside C and their unnatural analogs were successfully synthesized through a simple route. They were evaluated for their antiproliferative activity against human cervical epithelioid carcinoma cell lines. The preliminary screening results indicated that these compounds are potentially valuable source for new lead chemotherapeutics.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► First synthesis of helonioside A, 3′,4′,6′-tri-O-feruloylsucrose, lapathoside C. ► Synthesis of 17 unnatural PSEs. ► Significant antiproliferative activity (IC50 = 0.16 μM) against HeLa cell lines. ► Lipophilicity and number of feruloyl substituents affect the activity.