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

Abstract

A series of novel bivalent β-carbolines with a spacer of three to ten methylene units between the 3-carboxyl oxygens was synthesized and evaluated as antitumor agents. The results demonstrated that most compounds displayed good and selective cytotoxic activities against 769-P and KB cell lines. Acute toxicities and antitumor efficacies of the selected compounds in mice were also evaluated. Compound 22 exhibited potent antitumor activity against Lewis lung cancer in mice with a tumor inhibition rate of 64.2%. Preliminary structure–activity relationship analysis indicated that (1) the length of the spacer affected cytotoxic activities in vitro and six methylene units were more favorable; (2) the introduction of substituents into position-1 of the β-carboline ring might be detrimental to antitumor potency in vivo models.