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

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.

• Authors: Susanne Vogel, Doris Kaufmann, Michaela Pojarová, Christine Müller, Tobias Pfaller, Sybille Kühne, Patrick J Bednarski, Erwin von Angerer
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 16 Issue 12 Pg. 6436-47 (Jun 15 2008) ISSN: 1464-3391 [Electronic] England
• PMID: 18513974 (Publication Type: Journal Article)

Chemical References

• Antimitotic Agents
• Benzoates
• Hydrazones
• Indoles
• Pyridines
• Caspase 3

Topics

• Antimitotic Agents (chemical synthesis, chemistry, pharmacology)
• Benzoates (chemistry)
• Caspase 3 (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• Hydrazones (chemical synthesis, chemistry, pharmacology)
• Indoles (chemistry)
• Pyridines (chemistry)