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Biological Evaluation and Molecular Modelling Study of Podophyllotoxin Derivatives as Potent Inhibitors of Tubulin Polymerization
Author(s) -
Ma Yaqiong,
Fang Senbiao,
Li Huanhuan,
Han Chao,
Lu Yan,
Zhao Yonglong,
Liu Yingqian,
Zhao Chunyan
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12130
Subject(s) - podophyllotoxin , tubulin , microtubule , chemistry , colchicine , in vitro , microtubule polymerization , biochemistry , biophysics , stereochemistry , biology , microbiology and biotechnology , genetics
Microtubules are considered as important targets of anticancer therapy. Podophyllotoxin and its structural derivative are major microtubule‐interfering agents with potent anticancer activity. In this study, we reported the anticancer effects of 10 representative podophyllotoxin derivatives on a panel of four human cancer cell lines. Deoxypodophyllotoxin ( 6b ) and β‐apopicropodophyllotoxin ( 6g ) elicited strong antiproliferative effects ( IC 50 ) at a range of 0.0073–0.14 μ m . Direct tubulin depolymerization assay in vitro was also performed. Results showed that that the two compounds can inhibit microtubule polymerization. Experimental measurements were also supported by molecular dynamic simulations, which showed that the two active compounds formed interactions with the colchicine‐binding site of the tubulin protein. Our results helped us understand the nature of tubulin binding and determine the core design of a new series of potent inhibitors of tubulin polymerization.