title: AG11, a novel dichloroflavanone derivative with anti-mitotic activity towards human bladder cancer cells.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  AG11 appears to be an attractive scaffold for further development of a structurally simpler new anti-microtubule agents.
authors.affiliation: AGing Imaging Modeling, CNRS FRE 3405, Université Joseph Fourier, EPHE, Faculté de Médecine, BP 170 La Tronche, 38042 Grenoble Cedex, France. Veronique.Frachet@agim.eu.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Juhem
authors.forename: Ahcene
authors.initials: A
authors.lastname: Boumendjel
authors.forename: Bastien
authors.initials: B
authors.lastname: Touquet
authors.forename: Amandine
authors.initials: A
authors.lastname: Guillot
authors.forename: Andreï
authors.initials: A
authors.lastname: Popov
authors.forename: Xavier
authors.initials: X
authors.lastname: Ronot
authors.forename: Veronique
authors.initials: V
authors.lastname: Martel-Frachet
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001667:Binding, Competitive; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms
chemical_list: C584767:AG11 compound; D000970:Antineoplastic Agents; D044950:Flavanones; D050257:Tubulin Modulators; C505407:CASP3 protein, human; D053148:Caspase 3; D003078:Colchicine
keywords: Bladder carcinoma; antimitotic agents; cell cycle; flavanone; tubulin