Abstract
Four novel steroidal alkaloids named cortistatins A (1), B (2), C (3), and D (4) consisting of a 9(10-19)-abeo-androstane and isoquinoline skeleton have been isolated from the marine sponge Corticium simplex. The absolute stereostructures of 1-4 were elucidated by detailed 2D NMR, CD, and X-ray crystallographic analyses. Cortistatins A-D inhibited proliferation of human umbilical vein endothelial cells (HUVECs) with high selectivity. Among the four substances, cortistatin A (1) showed the strongest anti-proliferative activity (IC50 = 0.0018 muM) against HUVECs, in which the selective index was more than 3000-fold in comparison with that of normal fibroblast or several tumor cell lines.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / chemistry*
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Alkaloids / isolation & purification
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Alkaloids / pharmacology*
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Androstanes / chemistry*
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Androstanes / isolation & purification
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Androstanes / pharmacology*
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Angiogenesis Inhibitors / chemistry*
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Angiogenesis Inhibitors / isolation & purification
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Cell Growth Processes / drug effects
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Crystallography, X-Ray
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Endothelial Cells / cytology
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Endothelial Cells / drug effects
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Humans
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Molecular Structure
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Nuclear Magnetic Resonance, Biomolecular
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Porifera / chemistry
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Porifera / metabolism
Substances
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Alkaloids
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Androstanes
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Angiogenesis Inhibitors