Mar. Drugs 2008, 6(4), 514-527; doi:10.3390/md20080026
Article

Anticancer Alkaloid Lamellarins Inhibit Protein Kinases

1, 1, 1, 1, 2, 2, 3, 4 and 1,*
Received: 2 August 2008; in revised form: 18 September 2008 / Accepted: 26 September 2008 / Published: 8 October 2008
View Full-Text   |   Download PDF [627 KB, uploaded 6 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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.


Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert