[(2-Phenylindol-3-yl)methylene]propanedinitriles inhibit the growth of breast cancer cells by cell cycle arrest in G2/M phase and apoptosis

Cell cycle arrest of malignant cells is an important option for cancer treatment. In this study, we modified the structure of antimitotic 2-phenylindole-3-carbaldehydes by condensation with malononitrile. The resulting methylene propanedinitriles inhibited the growth of MDA-MB 231 and MCF-7 breast cancer cells with IC50 values below 100 nM. Though they exhibited similar structure–activity relationships as the aldehydes, they did not inhibit tubulin polymerization but were capable of blocking the cell cycle in G2/M phase. The cell cycle arrest was accompanied by apoptosis as demonstrated by the activation of caspases 3 and 9. Since the new 2-phenylindole derivatives also inhibited the growth of transplanted MXT mouse mammary tumors, they are interesting candidates for further development.

[(5-n-Alkyl-2-phenylindol-3-yl)methylene]propane-dinitriles strongly inhibit the growth of human breast cancer cells (IC50: 13–200 nM) by blockade of the cell cycle in G2/M phase.Figure optionsDownload as PowerPoint slide