Design, synthesis and biological evaluation of novel alkyl diamine linked bivalent β-carbolines as angiogenesis inhibitors

Bioorg Med Chem Lett. 2016 Oct 15;26(20):5065-5068. doi: 10.1016/j.bmcl.2016.08.084. Epub 2016 Aug 28.

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. Compound 2s was found to be the most potent antiproliferative agent with IC50 value of 1.06μM against EA.HY926 cell lines. Further investigations on mechanisms of action revealed that compound 2s significantly inhibited EA.HY926 cells migration and tube formation in a dose-dependent manner. Moreover compound 2s exhibited significant angiogenesis inhibitory effects in CAM assay, and the antiangiogenetic potency was comparable with the reference drug Endostar (30μM).

Keywords: Angiogenesis inhibitors; Antitumor; Bivalent β-carbolines; Structure–activity relationships; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / chemistry*
  • Angiogenesis Inhibitors / pharmacology*
  • Carbolines / chemical synthesis
  • Carbolines / chemistry*
  • Carbolines / pharmacology*
  • Drug Design
  • Human Umbilical Vein Endothelial Cells
  • Humans

Substances

  • Angiogenesis Inhibitors
  • Carbolines