Synthesis and cytotoxic evaluation of N2-benzylated quaternary β-carboline amino acid ester conjugates

Abstract The β-carboline alkaloids have been characterized as a class of potential antitumor agents. To further enhance the cytotoxic potency and improve water solubility of β-carboline, a series of new β-carboline amino acid ester, β-carboline amino acid and N 2 -benzylated quaternary β-carboline amino acid ester conjugates were designed and synthesized, and the cytotoxic activities of these compounds were evaluated using a panel of human tumor cell lines. The N 2 -benzylated quaternary β-carboline amino acid ester conjugates represented the most interesting cytotoxic activities. Particularly, compounds 8b and 8g were found to be the most potent compounds with IC 50 values lower than 20 μM against all human tumor cell lines investigated. These results confirmed that the N 2 -benzyl substituent on the β-carboline ring played an important role in the modulation of the cytotoxic potencies.