Synthesis and anti-tumor activities of methyl 2-O-aryl-6-O-aryl′-d-glucopyranosides

A synthetic method of introducing bulky aryl groups at the 2-O- and 6-O-positions on glucopyranosides was developed. A total of 37 new compounds of this class were obtained successfully. These compounds were tested on several tumor cell lines by MTT assays, and some of them exhibited encouraging inhibitory activities. The most potent compound, CAB-SHZH-27, exhibited EC50 values of 14, 12, and 10 μmol/L on A549, MDA-MB-231 and HeLa cells, respectively. A preliminary structure–activity relationship analysis indicates that the two free hydroxyl groups on the d-glucose core are indispensable for the biological activities of this class of compounds, and the aryl group at the 6-O-position has a more obvious impact than the one at the 2-O-position. An interesting ‘on–off’ mechanism of this class of compounds was also observed in our MTT assays, which remains to be explored.

Graphical abstractStructure of CAB-SHZH27 and its dose-dependent cytotoxicity on MDA-MB-231 cells.Figure optionsDownload full-size imageDownload as PowerPoint slide