Stictamides A鈭扖, MMP12 Inhibitors Containing 4-Amino-3-hydroxy-5-phenylpentanoic Acid Subunits

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• 作者：Zhibin Liang ; Analia Sorribas ; Florian J. Sulzmaier ; Jorge I. Jime虂nez ; Xin Wang ; Thomas Sauvage ; Wesley Y. Yoshida ; Guangyi Wang ; Joe W. Ramos ; Philip G. Williams
• 刊名：Journal of Organic Chemistry
• 出版年：2011
• 出版时间：May 20, 2011
• 年：2011
• 卷：76
• 期：10
• 页码：3635-3643
• 全文大小：934K
• 年卷期：v.76,no.10(May 20, 2011)
• ISSN：1520-6904

文摘

An extensive study of the secondary metabolites produced by a new Sticta sp. of lichen has led to the isolation of three new compounds containing the 4-amino-3-hydroxy-5-phenylpentanoic acid residue (Ahppa). The structures of stictamides A鈭扖 (1鈭?b>3) were assigned by 2D NMR spectroscopic and chemical methods. Due to extensive epimerization of the Ahppa residue observed after acid hydrolysis, the configuration of this unit was deduced through conversion of 1 to an appropriate derivative and application of our recently developed statine NMR database. Evaluation of stictamide A against a panel of disease-relevant proteases showed that it inhibited MMP12 at 2.3 渭M and significantly reduced invasion in the human glioma cell line U87MG. Docking studies suggest that stictamide A inhibits MMP12 by a non-zinc-binding mechanism.