Synthesis, cytotoxic activities and DNA binding properties of β-carboline derivatives

In a continuing effort to develop novel β-carbolines endowed with better pharmacological profile, a series of water-soluble β-carbolines bearing a flexible amino side chain was designed and synthesized, and the cytotoxic activities in vitro of these compounds were evaluated. The N9-arylated alkyl substituted β-carbolines represented the most interesting cytotoxic agents, and compounds 4c and 4d were found to be the most potent compounds with IC50 values lower than 10 μM against ten human tumor cell lines. The results confirmed that the N9-arylated alkyl substituents of β-carboline played a very important role in the modulation of the cytotoxic potencies. In addition, the interaction with DNA of these compounds was also investigated, these compounds were found to exhibit significant DNA binding affinity.

Graphical abstractA series of water-soluble β-carbolines bearing a flexible amino side chain was synthesized and evaluated. Compounds 4c and 4d were found to be the most potent compounds with IC50 values lower than 10 μM against ten tumor cell lines.Figure optionsDownload full-size imageDownload as PowerPoint slide