在基于探针的分子网络策略的指导下，从海洋海绵 Phakellia fusca 中分离出五种未描述的环七肽，Phakefusins A-E (1-5)。化合物 1 和 2 分别含有二氧吲哚基丙氨酸 (Dioia) 和 β-3-氧吲哚基丙氨酸 (Oia) 的非蛋白氨基酸残基。化合物 3 具有独特的甲硫氨酸亚砜，而化合物 5 包含谷氨酸乙酯单元。通过核磁共振波谱、HR-MS/MS 分析和先进的 Marfey 方法阐明了它们的结构。通过色氨酸氧化合成 (S, S/R)-Oia 标准品，我们使用先进的 Marfey 方法确定了化合物 2 中该氨基酸的构型。对这些环七肽的抗肿瘤、抗菌和抗氧化活性进行了评估。化合物 1 对 MCF-7 和 PC9 细胞表现出中等的细胞毒性，IC50 值分别为 6.8 和 9.6 μM，而化合物 2-5 通过上调 HO-1、NQO1 和 SOD2 水平以及诱导 Nrf2 表现出潜在的抗氧化作用激活。版权所有 © 2024。由 Elsevier Ltd 出版。

Guided by a probe-based molecular networking strategy, five undescribed cycloheptapeptides, phakefusins A-E (1-5), were isolated from the marine sponge Phakellia fusca. Compounds 1 and 2 contain the nonproteinogenic amino acid residues of dioxindolyalanine (Dioia) and β-3-oxindolylalanine (Oia), respectively. Compound 3 possesses a unique methionine sulfoxide, whereas compound 5 includes a glutamic acid ethyl ester unit. Their structures were elucidated through NMR spectroscopy, HR-MS/MS analysis, and the advanced Marfey's method. By synthesizing the (S, S/R)-Oia standard through tryptophan oxidation, we determined the configuration of this amino acid in compound 2 using the advanced Marfey's method. These cycloheptapeptides were evaluated for their antitumor, antibacterial, and antioxidant activities. Compound 1 showed moderate cytotoxicity against MCF-7 and PC9 cells, with IC50 values of 6.8 and 9.6 μM, respectively, while compounds 2-5 demonstrated potential antioxidant effects by upregulating HO-1, NQO1, and SOD2 levels, as well as inducing Nrf2 activation.Copyright © 2024. Published by Elsevier Ltd.