Aroyl hydrazones of 2-phenylindole-3-carbaldehydes as novel antimitotic agents.
Basic Information
ID: ALA1150769
Journal: Bioorg Med Chem
Title: Aroyl hydrazones of 2-phenylindole-3-carbaldehydes as novel antimitotic agents.
Authors: Vogel S, Kaufmann D, Pojarová M, Müller C, Pfaller T, Kühne S, Bednarski PJ, von Angerer E.
Abstract: 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 IC(50) 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 G(2)/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.
CiteXplore: 18513974
DOI: 10.1016/j.bmc.2008.04.071
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