Abstract
Aim: Identification of new anticancer glycosidic derivatives of podophyllotoxin. Methods: 14 podophyllotoxin D- and L-monosaccharides have been synthesized in three steps employing de novo 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 5j with tubulin was performed. Immunofluorescence was applied for detecting the inhibitory effect of 5j on tubulin polymerization. Results & conclusion: Most of synthesized compounds showed strong cytotoxicity activity against five cancer cell lines. Compound 5j possessed the highest cytotoxicity with the IC50 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 5j a higher binding affinity for tubulin.
Financial & competing interests disclosure
This work was supported by Natural Science Foundation of Nantong City (MS12017023-5) and Larger Instruments Open Foundation of Nantong University (KBJN1956). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.