AG11, a novel dichloroflavanone derivative with anti-mitotic activity towards human bladder cancer cells
Aurelie Juhem1, Ahcene Boumendjel, Bastien Touquet
1AGing Imaging Modeling, CNRS FRE 3405, Université Joseph Fourier, EPHE, Faculté de Médecine, BP 170 La Tronche, 38042 Grenoble Cedex, France. Veronique.Frachet@agim.eu.
Background:
New chemotherapy drugs should be investigated to improve survival of patients with advanced bladder cancer. Here, we report the synthesis and evaluation of AG11, a new flavanone derivative obtained through cyclization of its chalcone precursor CB11.
Materials And Methods:
The effect of AG11 on cell viability was evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay and apoptotic cell death was analyzed by flow cytometry. Finally, the effect of AG11 on tubulin polymerization in vitro and microtubule distribution across the cells was investigated.
Results:
AG11 was found to have an IC50 (half-maximal inhibitory concentration) of 4.6 μM and its inhibitory effect on RT4 cells proliferation is associated with a cell-cycle arrest in G2+M phases followed by apoptosis after a 48 h treatment. AG11 prevented polymerization of purified tubulin in a concentration-dependent manner in vitro and disrupted mitotic spindle formation in cells.
Conclusion:
AG11 appears to be an attractive scaffold for further development of a structurally simpler new anti-microtubule agents.
