Synthesis and biological evaluation of bivalent β-carbolines as potential anticancer agents

A series of novel bivalent beta-carbolines were synthesized and evaluated for their anti-proliferative activities on a panel of cancer cell lines, apoptosis induction and cell cycle effects. The present study showed that bivalent beta-carbolines possess stronger anti-proliferative effects than monomeric ones. Moreover, introduction of a methyl or benzyl group into the N-9 position of the bivalent beta-carbolines improved their antiproliferative activities. Additionally, the most potent compounds 4c and 8a with IC50 values of 0.84 mu M and 0.23 mu M, respectively, were more potent than doxorubicin (IC50 = 2.48 mu M) against A-549 cell lines. The most active compound 8a could induce cell apoptosis in a dose-dependent manner and cause cell cycle arrest in the S phase.