433969-28-9Relevant academic research and scientific papers
New C5-alkylated indolobenzazepinones acting as inhibitors of tubulin polymerization: Cytotoxic and antitumor activities
Keller, Laurent,Beaumont, Stéphane,Liu, Jian-Miao,Thoret, Sylviane,Bignon, Jér?me S.,Wdzieczak-Bakala, Joanna,Dauban, Philippe,Dodd, Robert H.
supporting information; experimental part, p. 3414 - 3421 (2009/05/26)
A series of 5-alkylindolobenzazepin-7-ones was synthesized by Suzuki coupling between 3-iodoindole-2-carboxylates and the appropriate α-alkylbenzylamino α-boronic acids followed by cyclization to the lactam. Derivatives having a linear alkyl chain at C5 were found to be highly cytotoxic to KB cells with IC50 values in the 30-80 nM range. These compounds also inhibited the polymerization of tubulin with IC50's of 1-2 μM. Compound 4f ((S)-5-ethyl) showed comparable antiproliferative activities (IC50's of 30-70 nM) in a variety of cancer cell lines, cell growth being arrested at the G2/M phase. Compound 4f induced apoptosis in a dose-dependent manner in three different cancer cell lines and was shown to affect cell morphology in a manner consistent with its inhibitory action on tubulin polymerization. Using the experimental model of glioma grafted on the chick chorio-allantoic membrane, local treatment with compound 4f markedly reduced tumor progression.
