Synthesis and Antiviral/Fungicidal/Insecticidal Activities Study of Novel Chiral Indole Diketopiperazine Derivatives Containing Acylhydrazone Moiety
Synthesis and Antiviral/Fungicidal/Insecticidal Activities Study of Novel Chiral Indole Diketopiperazine Derivatives Containing Acylhydrazone Moiety
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含酰腙结构的新型手性吲哚二酮哌嗪衍生物的合成及抗病毒/杀菌/杀虫活性研究
DOI：
10.1021/acs.jafc.0c00875
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发表时间：
2020-05-20
影响因子：
6.1
通讯作者：
Wang, Qingmin
中科院分区：
文献类型：
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作者：
Xie, Jialin;Xu, Wentao;Wang, Qingmin
根据酰腙类化合物抑制烟草花叶病毒CP组装的机理和哌嗪二酮环的独特结构特点，设计合成了一系列光学纯的吲哚哌嗪二酮酰腙类化合物。为了系统地研究化合物的空间构型对抗病毒活性的影响，我们还合成了4个C6和C12a位具有不同空间构型的化合物。生物测定结果表明，这些新化合物大多表现出中等至良好的抗病毒活性，其中化合物23、25、27、28、31和5d的活性明显高于市售三氮唑核苷。深入的构效关系研究表明，空间构象是调节抗病毒活性的重要因素之一，研究结果为该分子与靶蛋白相互作用的可能最佳构型提供了信息。同时，这些新化合物对14种植物病原真菌也表现出广谱的杀菌活性。部分化合物对小菜蛾和淡色库蚊具有较好的杀虫活性。
On the basis of the mechanism of acylhydrazone compounds inhibiting the assembly of TMV CP and the unique structural characteristics of diketopiperazine ring, a series of optically pure indole diketopiperazine acylhydrazone were designed and synthesized. In order to systematically study the effect of the spatial configuration of the compounds on the antiviral activity, four compounds with different spatial configurations at C6 and C12a were also prepared. The bioassay results indicated that most of these new compounds displayed moderate to good antiviral activity, among which compounds 23, 25, 27, 28, 31, and 5d showed a significantly higher activity than that of commercial ribavirin. An in-depth structure-activity relationship investigation showed that the spatial conformation was one of the most important factors in adjusting antiviral activity; the research results provided information about the possible optimum configuration for interaction of this molecular with its target protein. At the same time, these new compounds also exhibited broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi. What's more, some of these compounds exhibited good insecticidal activity to Plutella xylostella and Culex pipiens pallens.