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Design, synthesis, and biological evaluation of 2,3‐diphenyl‐cycloalkyl pyrazole derivatives as potential tubulin polymerization inhibitors
Author(s) -
Xia LinYing,
Yang Rong,
Zhang YaLiang,
Chu YiChun,
Qi YaLin,
Man RuoJun,
Wang ZhongChang,
Wang BaoZhong,
Zhu HaiLiang
Publication year - 2019
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.13565
Subject(s) - tubulin , hela , cytotoxicity , chemistry , apoptosis , pyrazole , in vitro , docking (animal) , microtubule , stereochemistry , cell culture , cell cycle , combinatorial chemistry , biochemistry , microbiology and biotechnology , biology , medicine , nursing , genetics
Several novel cycloalkyl‐fused 2,3‐diaryl pyrazole derivatives were designed, synthesized, and evaluated as potential anti‐tubulin agents. Compound A10 exhibited the most potent antiproliferative activity against a panel of cancer lines ( IC 50 = 0.78–2.42 μM) and low cytotoxicity against 293T & L02 ( CC 50 values of 131.74 and 174.89 μM, respectively). Moreover, A10 displayed inhibition of tubulin polymerization in vitro, arrested the G2/M phase of the cell cycle, changed morphology of tubulin, increased intracellular reactive oxygen species, and induced apoptosis of HeLa cells. Docking simulation and 3D‐ QSAR models were performed to elaborate on the anti‐tubulin mechanism of the derivatives. The inhibition of monoclonal colony formation provided more intuitional data to verify the possibility of A10 as a novel tubulin assembling inhibitor.