Anticancer Alkaloid Lamellarins Inhibit Protein Kinases

Marine Drugs

Dianne Baunbæk³  Nolwenn Trinkler³  Yoan Ferandin³  Olivier Lozach³  Poonsakdi Ploypradith²  Somsak Rucirawat²  Fumito Ishibashi¹  Masatomo Iwao⁴ 

[1] id="af1-marinedrugs-06-00514">1 C.N.R.S., Cell Cycle Group, Station Biologique, B.P. 74, 29682 Roscoff Cedex, Bretagne, Fran;Laboratory of Medicinal Chemistry, Chulaborhn Research Institute, Vipavadee-Rangsit Highway, Bangkok 10210, Thailand;C.N.R.S., Cell Cycle Group, Station Biologique, B.P. 74, 29682 Roscoff Cedex, Bretagne, France;Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan

关键词: lamellarin;    kinase inhibitor;    cyclin-dependent kinases;    CK1;    DYRK-1A;    GSK-3;   

DOI  :  10.3390/md20080026

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2008 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).