Synthesis and Antiviral/Fungicidal/Insecticidal Activities Study of Novel Chiral Indole Diketopiperazine Derivatives Containing Acylhydrazone Moiety

• Published in: Journal of agricultural and food chemistry 2020-05, Vol.68 (20), p.5555-5571
• Main Authors: Xie, Jialin, Xu, Wentao, Song, Hongjian, Liu, Yuxiu, Zhang, Jingjing, Wang, Qingmin
• Format: Article
• Language: English
• Subjects: Animals; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Culex - drug effects; Culex - growth & development; Diketopiperazines - chemistry; Diketopiperazines - pharmacology; Drug Design; Fungi - drug effects; Fungi - growth & development; Fungicides, Industrial - chemical synthesis; Fungicides, Industrial - chemistry; Fungicides, Industrial - pharmacology; Hydrazones - chemistry; Hydrazones - pharmacology; Indoles - chemistry; Indoles - pharmacology; Insecticides - chemical synthesis; Insecticides - chemistry; Insecticides - pharmacology; Lepidoptera - drug effects; Lepidoptera - growth & development; Molecular Structure; Structure-Activity Relationship; Tobacco Mosaic Virus - drug effects; Tobacco Mosaic Virus - growth & development
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.0c00875

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.