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Anticancer Alkaloid Lamellarins Inhibit Protein Kinases
C.N.R.S., Cell Cycle Group, Station Biologique, B.P. 74, 29682 Roscoff Cedex, Bretagne, France
Laboratory of Medicinal Chemistry, Chulaborhn Research Institute, Vipavadee-Rangsit Highway, Bangkok 10210, Thailand
Division of Marine Life Science and Biochemistry, Faculty of Fisheries, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14 Bunkyomachi, Nagasaki 852-8521, Japan
* Author to whom correspondence should be addressed.
Received: 2 August 2008; in revised form: 18 September 2008 / Accepted: 26 September 2008 / Published: 8 October 2008
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, dualspecificity 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.
Keywords: lamellarin; kinase inhibitor; cyclin-dependent kinases; CK1; DYRK-1A; GSK-3
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Baunbæk, D.; Trinkler, N.; Ferandin, Y.; Lozach, O.; Ploypradith, P.; Rucirawat, S.; Ishibashi, F.; Iwao, M.; Meijer, L. Anticancer Alkaloid Lamellarins Inhibit Protein Kinases. Mar. Drugs 2008, 6, 514-527.
Baunbæk D, Trinkler N, Ferandin Y, Lozach O, Ploypradith P, Rucirawat S, Ishibashi F, Iwao M, Meijer L. Anticancer Alkaloid Lamellarins Inhibit Protein Kinases. Marine Drugs. 2008; 6(4):514-527.
Baunbæk, Dianne; Trinkler, Nolwenn; Ferandin, Yoan; Lozach, Olivier; Ploypradith, Poonsakdi; Rucirawat, Somsak; Ishibashi, Fumito; Iwao, Masatomo; Meijer, Laurent. 2008. "Anticancer Alkaloid Lamellarins Inhibit Protein Kinases." Mar. Drugs 6, no. 4: 514-527.