Anticancer alkaloid lamellarins inhibit protein kinases.
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.
Baunbaek
Dianne
D
C.N.R.S., Cell Cycle Group, Station Biologique, Bretagne, France.
Trinkler
Nolwenn
N
Ferandin
Yoan
Y
Lozach
Olivier
O
Ploypradith
Poonsakdi
P
Rucirawat
Somsak
S
Ishibashi
Fumito
F
Iwao
Masatomo
M
Meijer
Laurent
L
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases