Anticancer Alkaloid Lamellarins Inhibit Protein Kinases

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2009 Jan 28

PMID 19172192

Citations 19

Authors

Dianne Baunbaek

Nolwenn Trinkler

Yoan Ferandin

Olivier Lozach

Poonsakdi Ploypradith

Somsak Rucirawat

Fumito Ishibashi

Masatomo Iwao

Laurent Meijer

Affiliations

Soon will be listed here.

Abstract

Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition of topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dual-specificity tyrosine phosphorylation activated kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good correlation is observed between the effects of lamellarins on protein kinases and their action on cell death, suggesting that inhibition of specific kinases may contribute to the cytotoxicity of lamellarins. Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors.

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