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Synthesis and Bioevaluation of Diphyllin Glycosides as Novel Anticancer Agents
Author(s) -
Zhao Yu,
Ni Chunyan,
Zhang Yuting,
Zhu Li
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201200035
Subject(s) - chemistry , glycoside , cytotoxicity , tubulin , stereochemistry , in vitro , glycosylation , topoisomerase , paclitaxel , microtubule , biochemistry , cancer , biology , genetics , microbiology and biotechnology
A series of diphyllin glycosides were synthesized from diphyllin by phase transfer catalysis glycosylation, deprotection, and etherification, and the structures were established by 1 H NMR, 13 C NMR, and HRMS. These glycosides were evaluated for their in vitro cytotoxicity against HCT‐116, A549, and A549T cancer cell lines by MTT assay, and most of them were cytotoxic at submicromolar concentrations. They were also effective against the paclitaxel‐resistant cell line A549T. The kDNA decatenation assay indicated that most of these compounds inhibited topoisomerase IIα‐mediated kDNA decatenation. In addition, the in vitro tubulin polymerization study showed that compounds 5 and 6 had antimicrotubule activity with a paclitaxel‐like mode of action. Taken together, these results suggest that these diphyllin glycosides act on both TopoII and tubulin.