通过分离一种新的(-)-(5)-(8)-(14)-麦角硫因类似物，进一步探究一种独特海绵来源的生物碱的性质。
Further Probing the Properties of a Unique Sponge-derived Alkaloid Through the Isolation of a New (-)-(5)-(8)-(14)-Mycothiazole Analogue.
机构信息
Department of Natural Sciences & Mathematics, Dominican University of California, San Rafael, California 94901, United States.
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California 90089, United States.
出版信息
J Nat Prod. 2024 Oct 25;87(10):2523-2529. doi: 10.1021/acs.jnatprod.4c00691. Epub 2024 Sep 30.
Scale-up isolation of (+)-(5)-(8)-(14)-mycothiazole () from Vanuatu specimens of to semisynthesize (+)-(5)-(8)-8--acetyl-(14)-mycothiazole () revealed a new diastereomer, (-)-(5)-(8)-(14)-mycothiazole (). The structure of was determined using HRMS, NMR, and comparing optical rotation to (-)-(5)-(8)-(14)-mycothiazole () and . The maximum tolerated dose of in mice was 0.1 mg/kg. The IC of in PANC-1 and HepG2 cancer cell lines was 111.6 and 115.0 nM. Evaluation of in showed similar oxygen consumption compared to -, and all compounds significantly increased the lifespan. The orientation at Δ is crucial for picomolar cytotoxicity but not for mitochondrial inhibition.
从瓦努阿图标本中大规模分离(+)-(5)-(8)-(14)-mycothiazole ()，以半合成(+)-(5)-(8)-8--acetyl-(14)-mycothiazole ()，揭示了一种新的非对映异构体(-)-(5)-(8)-(14)-mycothiazole ()。通过高分辨率质谱、核磁共振和比较(-)-(5)-(8)-(14)-mycothiazole ()和 ()的比旋光度确定了的结构。在小鼠中的最大耐受剂量为 0.1 mg/kg。在 PANC-1 和 HepG2 癌细胞系中的 IC 为 111.6 和 115.0 nM。在 中的评估表明，与 -相比，氧消耗相似，所有化合物都显著延长了寿命。在 Δ处的 取向对于皮摩尔细胞毒性至关重要，但对于线粒体抑制不重要。
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