Synthesis and preliminary evaluation of novel alkyl diamine linked bivalent β-carbolines as angiogenesis inhibitors

Abstract

A series of novel bivalent β-carbolines linked with an alkyl diamine spacer at the C-3 position were synthesized and evaluated as potent angiogenesis inhibitors. The results demonstrated that most bivalent β-carbolines displayed significant anti-proliferative effects against EA.HY926 human umbilical vein cell lines. Compound 8z was found to be the most potent anti-proliferative agent with an IC₅₀ value of 1.10 μM against EA.HY926 cell lines. Preliminary investigations on the mechanisms of action revealed that compound 8z could dramatically inhibit EA.HY926 cell migration and tube formation in a dose-dependent manner. Moreover, compound 8z exhibited significant angiogenesis inhibitory effects in CAM assay, and the anti-angiogenic potency was comparable with that of the reference drug Endostar. These molecules might serve as candidates for further development into vascular-targeting antitumor drugs.