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Issue 5, 2015
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Synthesis and evaluation of a series of resveratrol analogues as potent anti-cancer agents that target tubulin

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Abstract

A series of novel diarylacrylonitrile and trans-stilbene analogues of resveratrol has been synthesized and evaluated for their anticancer activities against a panel of 60 human cancer cell lines. The diarylacrylonitrile analogues 3b and 4a exhibited the most potent anticancer activity of all the analogues synthesized in this study, with GI50 values of <10 nM against almost all the cell lines in the human cancer cell panel. Compounds 3b and 4a were also screened against the acute myeloid leukemia (AML) cell line, MV4-11, and were found to have potent cytotoxic properties that are likely mediated through inhibition of tubulin polymerization. Results from molecular docking studies indicate a common binding site for 4a and 3b on the α,β-tubulin heterodimer, with a slightly more favorable binding for 4a compared to 3b; this is consistent with the results from the microtubule assays, which demonstrate that 4a is more potent than 3b in inhibiting tubulin polymerization in MV4-11 cells. Taken together, these data suggest that diarylacrylonitriles 3b and 4a may have potential as antitubulin therapeutics for treatment of both solid and hematological tumors.

Graphical abstract: Synthesis and evaluation of a series of resveratrol analogues as potent anti-cancer agents that target tubulin

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Supplementary files

Article information


Submitted
22 Oct 2014
Accepted
29 Jan 2015
First published
30 Jan 2015

Med. Chem. Commun., 2015,6, 788-794
Article type
Concise Article
Author version available

Synthesis and evaluation of a series of resveratrol analogues as potent anti-cancer agents that target tubulin

N. R. Madadi, H. Zong, A. Ketkar, C. Zheng, N. R. Penthala, V. Janganati, S. Bommagani, R. L. Eoff, M. L. Guzman and P. A. Crooks, Med. Chem. Commun., 2015, 6, 788
DOI: 10.1039/C4MD00478G

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