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

M. Gompel , M. Leost (1) , De Kier Joffe E. B. , L. Puricelli , Franco L. H. , J. Palermo , L. Meijer (1)

1 MCT - Molécules et cibles thérapeutiques

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.

Mots clés: Aminopyridines/*isolation & purification/pharmacology Animals Cell Division/drug effects/physiology Cell Line; Tumor Cell Survival/drug effects/physiology Comparative Study Dose-Response Relationship; Drug Enzyme Inhibitors/chemistry/*isolation & purification/*pharmacology Humans Indole Alkaloids/*isolation & purification/pharmacology Mice *Protein Kinase Inhibitors Research Support; Non-U.S. Gov't Urochordata/*enzymology

Domaines: Biochimie, Biologie Moléculaire

M. Gompel, M. Leost, De Kier Joffe E. B., L. Puricelli, Franco L. H., et al.. Meridianins, a new family of protein kinase inhibitors isolated from the ascidian Aplidium meridianum. Bioorganic and Medicinal Chemistry Letters, 2004, 14, pp.1703-1707. ⟨hal-00020119⟩