We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Biological Evaluation and Molecular Modelling Study of Podophyllotoxin Derivatives as Potent Inhibitors of Tubulin Polymerization.
- Authors
Ma, Yaqiong; Fang, Senbiao; Li, Huanhuan; Han, Chao; Lu, Yan; Zhao, Yonglong; Liu, Yingqian; Zhao, Chunyan
- Abstract
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 ( IC50) 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.
- Subjects
MICROTUBULES; PODOPHYLLOTOXIN; CANCER cells; POLYMERIZATION; COLCHICINE
- Publication
Chemical Biology & Drug Design, 2013, Vol 82, Issue 1, p12
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.12130