Design, synthesis and biological evaluation of novel alkyl diamine linked bivalent β-carbolines as angiogenesis inhibitors. Issue 20 (15th October 2016) - Chen, Qing
Graphical abstract: Highlights: A series of novel bivalent β-carbolines was prepared and evaluated as angiogenesis inhibitors. Compound2s was found to be the most potent antiangiogenetic agent. The length of the linker affected antiangiogenetic potency of bivalent β-carbolines. Abstract: A series of novel alkyl diamine linked bivalent β-carbolines was synthesized and evaluated for antiproliferative activity, inhibition of cell migration and tube formation, and anti-angiogenic activity in vivo. The results showed that most bivalent β-carbolines displayed significant antiproliferative effect against human umbilical vein cell lines EA.HY926. Compound2s was found to be the most potent antiproliferative agent with IC50 value of 1.06 μM against EA.HY926 cell lines. Further investigations on mechanisms of action revealed that compound2s significantly inhibited EA.HY926 cells migration and tube formation in a dose-dependent manner. Moreover compound2s exhibited significant angiogenesis inhibitory effects in CAM assay, and the antiangiogenetic potency was comparable with the reference drug Endostar (30 μM).