Symplocamide A, a Potent Cytotoxin and Chymotrypsin Inhibitor from the Marine Cyanobacterium Symploca sp.

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• 作者：Roger G. Linington ; Daniel J. Edwards ; Cynthia F. Shuman ; Kerry L. McPhail ; Teatulohi Matainaho ; William H. Gerwick
• 刊名：Journal of Natural Products
• 出版年：2008
• 出版时间：January 2008
• 年：2008
• 卷：71
• 期：1
• 页码：22 - 27
• 全文大小：121K
• 年卷期：v.71,no.1(January 2008)
• ISSN：1520-6025

文摘

Investigation of a Symploca sp. from Papua New Guinea has led to the isolation of symplocamide A (1), a potent cancer cell cytotoxin, which also inhibits serine proteases with a 200-fold greater inhibition of chymotrypsin over trypsin. The complete stereostructure of symplocamide A was determined by detailed NMR and MS analysis as well as chiral HPLC analysis of the component amino acid residues. The presence of several unusual structural features in symplocamide A provides new insights into the pharmacophore model for protease selectivity in this drug class and may underlie the potent cytotoxicity of this compound to H-460 lung cancer cells (IC₅₀ = 40 nM) as well as neuro-2a neuroblastoma cells (IC₅₀ = 29 nM).