Design, Synthesis and in vitro Antitumor Activities of Novel Bivalent β-Carbolines

A series of novel bivalent beta-carbolines with a spacer of three to ten methylene units between the 7-oxygen was synthesized and characterized by nuclear magnetic resonance (NMR) and mass spectrometry ( MS). The antitumor activities against Bel-7402, 786-0, BGC-823, A375, 769-P and MCF7 cell lines in vitro were investigated by MTT method. The results demonstrated that compounds 4c, 4k and 4r were almost inactive against all tumor cell lines, compounds 4g and 4o displayed significant cytotoxic activities with IC50 value of lower than 10 mu mol/L against all tumor cell lines. Most compounds displayed good and selective cytotoxic activities against HT-29 and Blu-87 cell lines. Primary structure-activity relationships ( SARs) analysis indicated that the length of the spacer affected cytotoxic activities in vitro, and 8-10 methylene units were more favorable. Moreover, n-butyl or i-butyl substituents in position-9 of beta-carboline facilitated the antitumor potencies.