Molecular diversity of trimethoxyphenyl-1,2,3-triazole hybrids as novel colchicine site tubulin polymerization inhibitors

Structurally diverse trimethoxyphenyl-1,2,3-triazole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three cancer cell lines (PC3, MGC803 and HepG2). Among them, trimethoxyphenyl-1,2,3-triazole containing the coumarin fragement 19c displayed better antip...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2019-03, Vol.165, p.309-322
Main Authors: Fu, Dong-Jun, Li, Ping, Wu, Bo-Wen, Cui, Xin-Xin, Zhao, Cheng-Bin, Zhang, Sai-Yang
Format: Article
Language:English
Subjects:
Apoptosis
Cell cycle
Colchicine site tubulin inhibitor
Coumarin
Trimethoxyphenyl-1,2,3-triazole
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Summary:Structurally diverse trimethoxyphenyl-1,2,3-triazole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three cancer cell lines (PC3, MGC803 and HepG2). Among them, trimethoxyphenyl-1,2,3-triazole containing the coumarin fragement 19c displayed better antiproliferative activity results with IC50 values from 0.13 μM to 1.74 μM than anticancer drug colchicine. Compound 19c could inhibit MGC803 cell growth and colony formation, induce G2/M phase arrest by down expression of CDK1, and promote apoptosis by regulating DR5 and Bcl-2 family. Moreover, 19c strongly inhibited tubulin polymerization by interacting with the colchicine site. [Display omitted] •Molecular diversity of trimethoxyphenyl-1,2,3-triazoles was explored.•19c inhibited colony formation against MGC803 cells at 30 nM.•19c arrested cell cycle at G2/M phase and induced apoptosis.•19c was a novel colchicine site tubulin polymerization inhibitor.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2019.01.033