In the search for antiviral cyclopeptides against influenza A virus, five unprecedented Caryophyllaceae-type cyclopeptides (1–5) were isolated from the leaves of Melicope pteleifolia. Their chemical structures and absolute configurations were unambiguously determined by means of advanced Marfey’s analysis and comprehensive spectroscopic analyses including two-dimensional nuclear magnetic resonance and MS/MS fragmentation. Interestingly, compounds 3–5 contain an unusual heterocycle, a 3a-hydroxypyrroloindole moiety, which was biosynthetically formed by a nucleophilic cyclization from the least abundant amino acid, tryptophan, precursor and has aroused a great interest in the aspect of chemical diversity and biological activity. All isolates (1–5) were evaluated for their protective effects against influenza A viruses H1N1 and H9N2 in MDCK cells. All isolated cyclopeptides exhibited strong anti-influenza activity, especially against H1N1. Compound 3 showed the most potent CPE inhibition effect, which was stronger than that of the positive control ribavirin against H1N1, with an EC₅₀ (μM) of 2.57 ± 0.45 along with higher selectivity.

中文翻译：

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Melicopteline A-E，不寻常的环肽生物碱具有抗病毒活性对来自甲型流感病毒蜜茱萸属pteleifolia

在寻求对A型流感病毒的抗病毒环肽，五前所未有石竹科型环肽（1 - 5）从叶片分离蜜茱萸属pteleifolia。它们的化学结构和绝对构型是通过先进的Marfey分析和包括二维核磁共振和MS / MS裂解在内的综合光谱学分析方法明确确定的。有趣的是，化合物3 - 5含有不寻常的杂环，即3a-羟基吡咯并吲哚部分，它是通过亲核环化反应由最少的氨基酸，色氨酸，前体生物合成而形成的，引起了人们对化学多样性和生物学活性的极大兴趣。所有分离物（1 - 5），用于在MDCK细胞中抗A型流感病毒H1N1和H9N2的保护作用进行了评价。所有分离的环肽均显示出强大的抗流感活性，尤其是针对H1N1的流感。化合物3表现出最强的CPE抑制作用，它比阳性对照病毒唑对H1N1的抑制作用更强，EC ₅₀（μM）为2.57±0.45，选择性更高。