Divergent synthesis of 2,4,5-trideoxyhexopyranosides derivatives of podophyllotoxin as anticancer agents.

Identification of new anticancer glycosidic derivatives of podophyllotoxin. 14 podophyllotoxin D- and L-monosaccharides have been synthesized in three steps employing glycosylation strategy, and their abilities to inhibit the growth of HeLa, HepG2, MCF-7, A549 and MDA-MB-231 cancer cells were investigated by MTT assay. Molecular docking study of compound with tubulin was performed. Immunofluorescence was applied for detecting the inhibitory effect of on tubulin polymerization. Most of synthesized compounds showed strong cytotoxicity activity against five cancer cell lines. Compound possessed the highest cytotoxicity with the IC values from 41.6 to 95.2 nM, and could concentration-dependently inhibit polymerization of the microtubule cytoskeleton of MCF-7 cells. Molecular docking disclosed that sugar moiety-dedicated hydrogen bond endowed a higher binding affinity for tubulin.