Melicopteline A-E, Unusual Cyclopeptide Alkaloids with Antiviral Activity against Influenza A Virus from Melicope pteleifolia
Melicopteline A-E, Unusual Cyclopeptide Alkaloids with Antiviral Activity against Influenza A Virus from Melicope pteleifolia
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DOI：
10.1021/acs.joc.0c02137
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发表时间：
2021-01-15
影响因子：
3.6
通讯作者：
Oh, Won Keun
中科院分区：
文献类型：
--
作者：
Lee, Ba Wool;Ha, Thi Kim Quy;Oh, Won Keun
在寻找抗甲型流感病毒的抗病毒环肽的过程中，从黄叶蜜草（Melicope pteleifolia）的叶中分离到五种前所未有的Cartilaceae型环肽（1-5）。它们的化学结构和绝对构型通过先进的Marvelt分析和全面的光谱分析，包括二维核磁共振和MS/MS碎片明确确定。有趣的是，化合物3-5含有一个不寻常的杂环，3a-羟基吡咯并吲哚部分，它是由最不丰富的氨基酸色氨酸前体通过亲核环化反应生物合成的，并且在化学多样性和生物活性方面引起了极大的兴趣。在MDCK细胞中评价所有分离株（1-5）对甲型流感病毒H1N1和H9 N2的保护作用。所有分离的环肽都表现出很强的抗流感病毒活性，尤其是抗H1N1。化合物3显示出最有效的CPE抑制作用，其比阳性对照利巴韦林对H1N1的CPE抑制作用更强，具有2.57 +/- 0.45沿着的EC 50（μ M）以及更高的选择性。
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 (mu M) of 2.57 +/- 0.45 along with higher selectivity.