期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 157, 期 -, 页码 1068-1080出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2018.08.074
关键词
Tubulin inhibitors; Vinyl sulfone; Colchicine binding site; Anti-tumor activity
资金
- National Natural Science Foundation of China [81673306, 81703348]
- Open Project of State Key Laboratory of Natural Medicines, China Pharmaceutical University [SKLNMKF 201710]
Vinyl sulfone or sulfoxide moieties were firstly introduced to the structure of chalcone compound by replacing the carbonyl group to afford a series of novel compounds as potential anti-tubulin agents. All of the target compounds were evaluated for their anti-proliferative activity. Among them, compound 12m showed the most potent activity against a panel of cancer cell lines with IC50 values ranging from 0.128 to 0.606 mu M. Further mechanism studies demonstrated that compound 12m caused G2/M phase arrest, induced cell apoptosis and disrupted the intracellular microtubule network. Moreover, compound 12m reduced the cell migration and disrupted the capillary-like tube formation in human umbilical vein endothelial cell (HUVEC) assays. Importantly, compound 12m significantly and dose dependently inhibited tumor growth in H22 liver cancer allograft mouse model, which is more potent than control compound CA-4, suggesting that 12m deserves further research as a potential anti-tubulin agent targeting colchicine binding site on tubulin. (C) 2018 Elsevier Masson SAS. All rights reserved.
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