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Synthesis and Biological Evaluations of 1,2‐Diaryl Pyrroles as Analogues of Combretastatin A‐4
Author(s) -
Sun Jun,
Chen Lei,
Liu Chunjiang,
Wang Zhan,
Zuo Daiying,
Pan Jiatong,
Qi Huan,
Bao Kai,
Wu Yingliang,
Zhang Weige
Publication year - 2015
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.12617
Subject(s) - combretastatin , tubulin , microtubule , chemistry , stereochemistry , colchicine , cell culture , dimer , docking (animal) , ic50 , microtubule polymerization , cancer cell lines , cancer cell , in vitro , biochemistry , biology , cancer , organic chemistry , microbiology and biotechnology , medicine , genetics , nursing
A series of novel 1,2‐diaryl pyrroles as analogues of combretastatin A‐4 ( CA‐4, 1a ) were synthesized and evaluated for their antitumour potential against three cancer cell lines. Most compounds exhibited growth inhibition against all of the cancer cell lines. Compound 7q not only exhibited prominent antitumour efficacy with IC 50 values of 0.390 μ m in SGC ‐7901, 0.070 μ m in HT ‐1080 and 0.045 μ m in KB cell lines but also showed low activity with IC 50 values of 30.08 μ m in normal L929 cell line. Moreover, compound 7q inhibited tubulin polymerization into microtubules and caused microtubule destabilization. A molecular docking study of 7q was performed to determine its binding mode at the colchicine site in the tubulin dimer.