A series of water-soluble beta-carbolines, bearing a flexible amino side chain, was prepared and evaluated in vitro against a panel of human tumor cell lines. The N(9)-arylated alkyl substituted beta-carbolines represented the most interesting cytotoxic activities, and compound 7b was found to be the most potent antitumor agent with IC(50) values lower than 10microM against eight human tumor cell lines. The results confirmed that the N(9)-arylated alkyl substituents of beta-carboline nucleus played an important role in the modulation of the cytotoxic potencies. In addition, these compounds were found to exhibit significant DNA-binding affinity.