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

摘要

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 IC(50) values lower than 10 muM 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.