Syntheses and Biological Activity of Amamistatin B and Analogs

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• 作者：Kelley A. Fennell ; Ute M&ouml ; llmann ; Marvin J. Miller
• 刊名：Journal of Organic Chemistry
• 出版年：2008
• 出版时间：February 1, 2008
• 年：2008
• 卷：73
• 期：3
• 页码：1018 - 1024
• 全文大小：144K
• 年卷期：v.73,no.3(February 1, 2008)
• ISSN：1520-6904

文摘

Amamistatins A and B, natural products isolated from a strain of Nocardia, showed growth inhibitionagainst three human tumor cell lines (IC₅₀ 0.24-0.56 M). Structurally related mycobactins affect thegrowth of both mycobacterial and human cells through interference with iron chelation. To further probethe biological activity of this class of compounds, the total syntheses of amamistatin B and two analogswere completed, and the synthetic samples were screened for tumor cell growth inhibition, HDACinhibition, and Mycobacterium tuberculosis growth inhibition. Amamistatin B (15) and diastereomer 18were both active against MCF-7 cells (IC₅₀ 0.12-0.20 M), and less so against PC-3 cells (IC₅₀ 8-13M). Amamistatin B only moderately inhibited the growth of M. tuberculosis (MIC 47 M) but showedgrowth promotion of Mycobacterium smegmatis and other bacteria.