Premium
Synthesis and Biological Evaluation of Boronic Acid Containing cis ‐Stilbenes as Apoptotic Tubulin Polymerization Inhibitors
Author(s) -
Nakamura Hiroyuki,
Kuroda Hirokazu,
Saito Hiroyuki,
Suzuki Ryo,
Yamori Takao,
Maruyama Kazuo,
Haga Tatsuya
Publication year - 2006
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200600068
Subject(s) - chemistry , boronic acid , combretastatin , tubulin , stereochemistry , apoptosis , polymerization , ring (chemistry) , microtubule , combinatorial chemistry , biochemistry , organic chemistry , biology , microbiology and biotechnology , polymer
A series of boronic acid containing cis ‐stilbenes as potent inhibitors of tubulin polymerization was synthesized by the introduction of boronic acid as an acceptor‐type functional group into the aromatic ring B of the combretastatin framework. High cell‐growth inhibition was observed with boron compounds 13 c and 13 d , in which a hydroxy group on the aromatic ring B of combretastatin A‐4 was replaced with boronic acid; IC 50 values toward B‐16 and 1‐87 cell lines are 0.48–2.1 μ M . Compounds 13 c and 13 d exhibited significant inhibitory activity toward tubulin polymerization (IC 50 =21–22 μ M ). The carboxylic acid derivative 17 , which can be considered as a mimic of boronic acid 13 c , did not show significant inhibition of cell growth or tubulin polymerization. According to the FACScan analysis using Jurkat cells, apoptosis was induced after incubation for 8 h with 13 c at a concentration of >10 −8 M . Growth inhibitory experiments against a panel of 39 human cancer cell lines revealed 13 c to inhibit growth differently than combretastatin A‐4; the correlation coefficient ( r ) between the two compounds was 0.553 in the COMPARE analysis.