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

In a continuing effort to develop novel beta-carbolines endowed with better pharmacological profile, a series of water-soluble beta-carbolines bearing a flexible amino side chain was designed and synthesized, and the cytotoxic activities in vitro of these compounds were evaluated. The N-9-arylated alkyl substituted beta-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 mu M against ten human tumor cell lines. The results confirmed that the N-9-arylated alkyl substituents of beta-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. (C) 2010 Elsevier Masson SAS. All rights reserved.