Synthesis and antitumor activities of 1-(4-chlorophenyl)-β-carboline derivatives

The starting material L-tryptophan reacted with 4-chlorobenzaldehyde via Pictet-Spengler condensation and followed by oxidation and decarboxylation to afford the 1-(4-chlorophenyl)-β-carboline.  The intermediate was further reacted with alkyl halogenide by N⁹-alkylation and N²-quaternarization to obtain 12 novel 1-(4-chlorophenyl)-β-carboline derivatives.  The chemical structures of all target compounds were characterized by elemental analyses, MS and ¹H NMR spectra.  The antitumor activities of the target compounds were evaluated by MTT method.  The results demonstrated that N²-quaternarized compounds enhanced the antitumor activity significantly.  In particular, compound 15 was found to be the most potent compound with IC₅₀ values lower than 5 μmol·L⁻¹ against 6 human tumor cells.  These results confirmed that the N²-alkyl or aralkyl substituent on the β-carboline ring played an important role in the modulation of the antitumor activities.