Abstract
The gerronemins A-F (1-6) were isolated as the cytotoxic components of an extract of a Gerronema species detected in a screening for new cytotoxic metabolites from basidiomycetes. Their structures were elucidated by spectroscopic techniques, and they are composed of a C12-C16 alkane or alkene substituted at both ends by 2,3-dihydroxyphenyl groups. The gerronemins blocked the inducible expression of a hCOX-2 and iNOS promoter driven reporter gene with IC50-values of 1-5 microg/ml. In addition, cytotoxic activities were observed which were due the inhibition of cellular macromolecular syntheses.
MeSH terms
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Agaricales / chemistry*
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Alkanes / chemistry
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Alkanes / isolation & purification
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Alkanes / pharmacology
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Alkenes / chemistry
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Alkenes / isolation & purification
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Alkenes / pharmacology
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Animals
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Catechols / chemistry
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Catechols / isolation & purification
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Catechols / pharmacology*
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Cell Survival / drug effects
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Cells, Cultured
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Cyclooxygenase 2
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Gene Expression / drug effects*
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Genes, Reporter
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HL-60 Cells
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Humans
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Isoenzymes / genetics
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Jurkat Cells
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Membrane Proteins
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Molecular Conformation
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase Type II
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Promoter Regions, Genetic
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Prostaglandin-Endoperoxide Synthases / genetics
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Tumor Cells, Cultured
Substances
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Alkanes
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Alkenes
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Catechols
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Isoenzymes
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Membrane Proteins
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NOS2 protein, human
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases