Aroyl hydrazones of 2-phenylindole-3-carbaldehydes as novel antimitotic agents

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 hydrazides of various benzoic and pyridine carboxylic acids. The resulting hydrazones inhibited the growth of MDA-MB 231 and MCF-7 breast cancer cells with IC50 values of 20–30 nM for the most potent derivatives. These 2-phenylindole derivatives also exerted an inhibitory effect on the growth of both proliferating and resting U-373 MG glioblastoma cells. Though the hydrazones exhibited similar structure–activity relationships as the aldehydes, they did not inhibit tubulin polymerization as the aldehydes 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 caspase-3. Since these 2-phenylindole-based hydrazones display no structural similarity with other antitumor drugs they are interesting candidates for further development.

5-Butyl-2-(4-methoxyphenyl)indole-3-carbaldehyde aroyl hydrazones strongly inhibit the growth of human breast cancer cells (IC50, 19–115 nM) by cell cycle arrest in G2/M phase and apoptosis.Figure optionsDownload as PowerPoint slide