A “natural” approach: Synthesis and cytoxicity of monodesmosidic glycyrrhetinic acid glycosides

•In this study we synthesized and investigated monodesmosidic glycyrrhetinic acid glycosides.•The compounds were tested for their antitumor activity using human cancer cell lines.•Many of the compounds are cytotoxic.•The compounds act by apoptosis.

Several pentacyclic triterpenoic acids have shown noteworthy antitumor activity, among them betulinic acid as well as oleanolic acid and derivatives thereof. Glycyrrhetinic acid (GA) exhibits some cytotoxic activity albeit this compound is not as active as betulinic acid, but GA came in the focus of scientific interest since it triggers apoptosis in tumor cells. In addition, it can be extracted from the roots of liquorice in high yields. Previous studies revealed that the introduction of an extra hydrophilic moiety increases the cytotoxicity of these compounds. Thus, a series of GA glycosides was prepared utilizing hexoses as well as pentoses (in d- and l-configuration) by using glycosyl trichloroacetimidates and TMSOTf as catalyst. The compounds were screened for cytotoxic activity against seven human cancer cell lines and the not malignant murine cell line NIH 3T3using a photometric SRB assay. The compounds trigger apoptosis as shown from extra trypan blue and acridine orange/ethidium bromide staining.

Graphical abstractSeveral novel monodesmosidic derivatives of methyl glycyrrhetinate were prepared. They were shown to be cytotoxic against several human tumor cell lines and to trigger apoptotic cell death.Figure optionsDownload full-size imageDownload as PowerPoint slide