Synthesis and biological evaluation of 4 arylcoumarin analogues as tubulin-targeting antitumor agents
Date
2017Author
Mutai, Peggoty
Breuzard, Gilles
Pagano, Alessandra
Allegro, Diane
Peyrot, Vincent
Chibale, Kelly
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
The synthesis of twenty-six 4-arylcoumarin analogues of combretastatin A-4 (CA-4) led to the identification of two new compounds (25 and 26) with strong cytotoxic activity. Both compounds had a high cytotoxic effect on a CA-4-resistant colon adenocarcinoma cell line (HT29D4). The compounds affected cell cycle progression characterized by a mitotic block. The activity of these compounds against microtubules both in vitro and in cells was examined and both compounds were found to potently inhibit in vitro microtubule formation via a sub-stoichiometric mode like CA-4. By immunofluorescence, it was observed that both compounds induced strong microtubule network disruption. Our results provide a strong experimental basis to develop new potent anti-tubulin molecules targeting CA-4-resistant cancer cells.
URI
http://www.sciencedirect.com/science/article/pii/S0968089616310732http://hdl.handle.net/11295/100751
Citation
Bioorganic & Medicinal Chemistry Volume 25, Issue 5, 1 March 2017, Pages 1652–1665Publisher
University of Nairobi
Collections
- Faculty of Health Sciences (FHS) [10377]