Abstract
Raf/MEK-1/MAPK cascade inhibitor activity-directed fractionation of the sponge Stylissa massa afforded eight known alkaloids: aldisine (1), 2-bromoaldisine (2), 10Z-debromohymenialdisine (3), 10E-hymenialdisine (4), 10Z-hymenialdisine (5), hymenin (6), oroidin (7), and 4,5-dibromopyrrole-2-carbonamide (8). Both 4 and 5 showed significant enzyme inhibitory activity (IC(50) 3 and 6 nM, respectively). Secondary assays identified these compounds as potent MEK-1 inhibitors. Compounds 4 and 5 also inhibited the growth of human tumor LoVo cells.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antineoplastic Agents / isolation & purification
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Antineoplastic Agents / pharmacology*
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Azepines / isolation & purification
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Azepines / pharmacology*
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology*
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Enzyme-Linked Immunosorbent Assay
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Humans
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
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Philippines
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Phosphorylation
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Porifera / chemistry*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Pyrroles / isolation & purification
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Pyrroles / pharmacology*
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Azepines
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Enzyme Inhibitors
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Pyrroles
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hymenialdisine
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Protein Serine-Threonine Kinases
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MAP Kinase Kinase 1
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MAP2K1 protein, human
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Mitogen-Activated Protein Kinase Kinases