Structures of Nahuoic Acids B–E Produced in Culture by a Streptomyces sp. Isolated from a Marine Sediment and Evidence for the Inhibition of the Histone Methyl Transferase SETD8 in Human Cancer Cells by Nahuoic Acid A

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• 作者：David E. Williams ; Fanny Izard ; Stéphanie Arnould ; Doralyn S. Dalisay ; Cholpisut Tantapakul ; Wisanu Maneerat ; Teatulohi Matainaho ; Eric Julien ; Raymond J. Andersen
• 刊名：Journal of Organic Chemistry
• 出版年：2016
• 出版时间：February 19, 2016
• 年：2016
• 卷：81
• 期：4
• 页码：1324-1332
• 全文大小：427K
• ISSN：1520-6904

文摘

Nahuoic acids A–E (<b>1b>–<b>5b>) have been isolated from laboratory cultures of a Streptomyces sp. obtained from a tropical marine sediment. The structures of the new polyketides <b>2b>–<b>5b> were elucidated by analysis of spectroscopic data of the natural products and the chemical derivatives <b>6b> and <b>7b>. Nahuoic acids <b>1b>–<b>5b> are in vitro inhibitors of the histone methyltransferase SETD8, and nahuoic acid A (<b>1b>) and its pentaacetate derivative <b>8b> inhibit the proliferation of several cancer cells lines in vitro with modest potency. At the ICb>50b> for cancer cell proliferation, nahuoic acid A (<b>1b>) showed selective inhibition of SETD8 in U2OS osteosarcoma cells that reflect its selectivity against a panel of pure histone methyl transferases. A cell cycle analysis revealed that the cellular toxicity of nahuoic acid A (<b>1b>) is likely linked to its ability to inhibit SETD8 activity.