Design, synthesis and cytotoxicity evaluation of indibulin analogs

Abstract

AbstractIndibulin is one of the most potent tubulin polymerization inhibitors with minimal peripheral neuropathy. The design and synthesis of new indibulin analogs were carried out in order to investigate their anti-cancer activity. The target compounds 4a–i were synthesized in multistep reactions starting with the related indole derivatives. Compound 4f shows the highest cytotoxic activity on HT-29 and Caco-2 cell lines with the respective half maximal inhibitory concentration (IC50) values of 5.1 μm and 7.3 μm. In the case of the T47-D cell line, compound 4c exerts the best cytotoxic activity with an IC50 value of 11.5 μm. In the cell cycle analysis on HT-29 cells, compound 4f at 5.1 μm showed an increase in the percentage of cells in the sub-G1 phase. Altogether, nine target compounds were synthesized and characterized by infrared spectroscopy (IR), proton nuclear magnetic resonance (1H NMR), carbon-13 nuclear magnetic resonance (13C NMR), mass spectrometry (MS) and elemental analysis. Some of the compounds show good cytotoxic activity against cancerous cell lines.