2-Arylidenedihydroindole-3-ones: design, synthesis, and biological activity on bladder carcinoma cell lines.
2-Arylidenedihydroindole-3-ones were assayed for their antiproliferative and apoptotic abilities as potential drug candidates to treat bladder tumor. These compounds were tested on cell lines obtained from bladder tumors of various stages [superficial (pTa and pT1) vs. invasive (pT2)]. The most active compound (3c) inhibited the proliferation, induced apoptosis, and decreased the expression of p-Stat5 and p-Pyk2 in DAG-1 and RT112 lines in which the FGFR3 is either mutated or overexpressed. Knowing that FGFR3 is involved in cell proliferation, differentiation, and migration through cell signaling pathways including p-Stat5 way via p-Pyk2, let us assume that compound 3c may probably act through FGFR3 pathway.
Gerby
Bastien
B
Laboratoire de Dynamique Cellulaire, EPHE, UMR-CNRS 5525, IFRT 130, Université Joseph Fourier, Pavillon Taillefer, 38706 La Tronche Cedex, France.
Boumendjel
Ahcène
A
Blanc
Madeleine
M
Bringuier
Pierre Paul
PP
Champelovier
Pierre
P
Fortuné
Antoine
A
Ronot
Xavier
X
Boutonnat
Jean
J
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009367:Neoplasm Staging; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000037:antagonists & inhibitors*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000473:pathology
C519009:4,6-dimethoxy-2-(2-fluorobenzylidene)-3(2H)-indolone; D000970:Antineoplastic Agents; D007211:Indoles; D050799:STAT5 Transcription Factor; D051498:Receptor, Fibroblast Growth Factor, Type 3; D051418:Focal Adhesion Kinase 2