Meridianins, a new family of protein kinase inhibitors isolated from the ascidian Aplidium meridianum

Bioorg Med Chem Lett. 2004 Apr 5;14(7):1703-7. doi: 10.1016/j.bmcl.2004.01.050.

Abstract

Meridianins are brominated 3-(2-aminopyrimidine)-indoles which are purified from Aplidium meridianum, an Ascidian from the South Atlantic (South Georgia Islands). We here show that meridianins inhibit various protein kinases such as cyclin-dependent kinases, glycogen synthase kinase-3, cyclic nucleotide-dependent kinases and casein kinase 1. Meridianins prevent cell proliferation and induce apoptosis, a demonstration of their ability to enter cells and to interfere with the activity of kinases important for cell division and cell death. These results suggest that meridianins constitute a promising scaffold from which more potent and selective protein kinase inhibitors could be designed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / isolation & purification*
  • Aminopyridines / pharmacology
  • Animals
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Indole Alkaloids / isolation & purification*
  • Indole Alkaloids / pharmacology
  • Mice
  • Protein Kinase Inhibitors*
  • Urochordata / enzymology*

Substances

  • Aminopyridines
  • Enzyme Inhibitors
  • Indole Alkaloids
  • Protein Kinase Inhibitors