The spirooxepinisoxazoline alkaloid psammaplysin F (1) was selected as a scaffold for the generation of a unique screening library for both drug discovery and chemical biology research. Large-scale extraction and isolation chemistry was performed on a marine sponge (Hyattella sp.) collected from the Great Barrier Reef in order to acquire >200 mg of the desired bromotyrosine-derived alkaloidal scaffold. Parallel solution-phase semisynthesis was employed to generate a series of psammaplysin-based urea (2–9) and amide analogues (10–11) in low to moderate yields. The chemical structures of all analogues were characterized using NMR and MS data. The absolute configuration of psammaplysin F and all semisynthetic analogues was determined as 6R, 7R by comparison of ECD data with literature values. All compounds (1–11) were evaluated for their effect on cell cycle distribution and changes to cancer metabolism in LNCaP prostate cancer cells using a multiparametric quantitative single-cell imaging approach. These investigations identified that in LNCaP cells psammaplysin F and some urea analogues caused loss of mitochondrial membrane potential, fragmentation of the mitochondrial tubular network, chromosome misalignment, and cell cycle arrest in mitosis.

中文翻译：

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通过多参数定量单细胞成像合成独特的 Psammaplysin F 文库和前列腺癌细胞的功能评估。

螺氧杂异恶唑啉生物碱 psammaplysin F ( 1 ) 被选为支架，用于生成用于药物发现和化学生物学研究的独特筛选库。对从大堡礁收集的海海绵 ( Hyattella sp.)进行大规模提取和分离化学，以获得 > 200 mg 所需的溴酪氨酸衍生生物碱支架。平行液相半合成被用来生成一系列基于 psammalysin 的尿素 ( 2 – 9 ) 和酰胺类似物 ( 10 – 11)) 中低收益率。使用NMR和MS数据表征所有类似物的化学结构。通过将 ECD 数据与文献值进行比较，将 psammaplysin F 和所有半合成类似物的绝对构型确定为 6 R、7 R。使用多参数定量单细胞成像方法评估了所有化合物 ( 1 – 11 ) 对细胞周期分布和 LNCaP 前列腺癌细胞中癌症代谢变化的影响。这些研究发现，在 LNCaP 细胞中，蛋白酶解蛋白酶 F 和一些尿素类似物会导致线粒体膜电位的丧失、线粒体管网络的断裂、染色体错位和有丝分裂中的细胞周期停滞。