{"title":"偶氮氨基嘧啶衍生物作为鳞翅目排他几丁质酶抑制剂的合理设计","authors":"Baokang Ding, Shujie Ma, Meiling Yang, Quanguo Zhang, Xiujia Hua, Jiahao Zhang, Shenmeng Bai, Lihui Zhang, Jingao Dong, Shengqiang Shen, Lili Dong","doi":"10.1111/pbi.14538","DOIUrl":null,"url":null,"abstract":"<i>Ostrinia furnacalis</i> (<i>O. furnacalis</i>) is a commonly occurring agricultural pest that can severely impact corn yield and quality. Therefore, establishing and implementing effective control methods against <i>O. furnacalis</i> are of great significance. Chemical insecticides remain the most effective means to mitigate the damage caused by <i>O. furnacalis</i>. With the increasing resistance of <i>O. furnacalis</i> to insecticides, it is imperative to identify and develop compounds with novel mechanisms of action and high safety. The chitinase O<i>f</i>Chi-h, identified and characterized in <i>O. furnacalis</i>, has been recognized as a potential insecticide target. In this study, a series of azo-aminopyrimidine analogues were synthesized as O<i>f</i>Chi-h inhibitors employing rational molecular optimization. Among them, compounds <b>9b</b>, <b>10a</b> and <b>10g</b> exhibited <i>K</i><sub>i</sub> values of 23.2, 19.4, and 43.2 nM against O<i>f</i>Chi-h, respectively. Molecular docking studies were carried out to explore the molecular basis for the high efficacy of these compounds and O<i>f</i>Chi-h. In addition, the morphological changes of the cuticle in inhibitor-treated <i>O. furnacalis</i> larvae were assessed using scanning electron microscopy. Furthermore, the target compounds were assayed in leaf dipping and pot experiments, with compound <b>10a</b> exhibiting greater insecticidal activity against <i>Plutella xylostella</i> (<i>P. xylostella</i>) and <i>O. furnacalis</i> than diflubenzuron and chlorbenzuron. At the same time, the toxicity of these compounds to natural enemies <i>Trichogramma ostriniae</i> and rats was negligible. The present study demonstrates that the azo-aminopyrimidine skeleton can be used as a novel, low-cost scaffold for developing insect chitinolytic enzyme inhibitors, with the potential to be utilized as new environmentally friendly insecticides.","PeriodicalId":221,"journal":{"name":"Plant Biotechnology Journal","volume":"9 1","pages":""},"PeriodicalIF":10.1000,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rational design of azo-aminopyrimidine derivatives as the potent lepidoptera-exclusive chitinase inhibitors\",\"authors\":\"Baokang Ding, Shujie Ma, Meiling Yang, Quanguo Zhang, Xiujia Hua, Jiahao Zhang, Shenmeng Bai, Lihui Zhang, Jingao Dong, Shengqiang Shen, Lili Dong\",\"doi\":\"10.1111/pbi.14538\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<i>Ostrinia furnacalis</i> (<i>O. furnacalis</i>) is a commonly occurring agricultural pest that can severely impact corn yield and quality. Therefore, establishing and implementing effective control methods against <i>O. furnacalis</i> are of great significance. Chemical insecticides remain the most effective means to mitigate the damage caused by <i>O. furnacalis</i>. With the increasing resistance of <i>O. furnacalis</i> to insecticides, it is imperative to identify and develop compounds with novel mechanisms of action and high safety. The chitinase O<i>f</i>Chi-h, identified and characterized in <i>O. furnacalis</i>, has been recognized as a potential insecticide target. In this study, a series of azo-aminopyrimidine analogues were synthesized as O<i>f</i>Chi-h inhibitors employing rational molecular optimization. Among them, compounds <b>9b</b>, <b>10a</b> and <b>10g</b> exhibited <i>K</i><sub>i</sub> values of 23.2, 19.4, and 43.2 nM against O<i>f</i>Chi-h, respectively. Molecular docking studies were carried out to explore the molecular basis for the high efficacy of these compounds and O<i>f</i>Chi-h. In addition, the morphological changes of the cuticle in inhibitor-treated <i>O. furnacalis</i> larvae were assessed using scanning electron microscopy. Furthermore, the target compounds were assayed in leaf dipping and pot experiments, with compound <b>10a</b> exhibiting greater insecticidal activity against <i>Plutella xylostella</i> (<i>P. xylostella</i>) and <i>O. furnacalis</i> than diflubenzuron and chlorbenzuron. At the same time, the toxicity of these compounds to natural enemies <i>Trichogramma ostriniae</i> and rats was negligible. The present study demonstrates that the azo-aminopyrimidine skeleton can be used as a novel, low-cost scaffold for developing insect chitinolytic enzyme inhibitors, with the potential to be utilized as new environmentally friendly insecticides.\",\"PeriodicalId\":221,\"journal\":{\"name\":\"Plant Biotechnology Journal\",\"volume\":\"9 1\",\"pages\":\"\"},\"PeriodicalIF\":10.1000,\"publicationDate\":\"2024-12-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Plant Biotechnology Journal\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1111/pbi.14538\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Plant Biotechnology Journal","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1111/pbi.14538","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Rational design of azo-aminopyrimidine derivatives as the potent lepidoptera-exclusive chitinase inhibitors
Ostrinia furnacalis (O. furnacalis) is a commonly occurring agricultural pest that can severely impact corn yield and quality. Therefore, establishing and implementing effective control methods against O. furnacalis are of great significance. Chemical insecticides remain the most effective means to mitigate the damage caused by O. furnacalis. With the increasing resistance of O. furnacalis to insecticides, it is imperative to identify and develop compounds with novel mechanisms of action and high safety. The chitinase OfChi-h, identified and characterized in O. furnacalis, has been recognized as a potential insecticide target. In this study, a series of azo-aminopyrimidine analogues were synthesized as OfChi-h inhibitors employing rational molecular optimization. Among them, compounds 9b, 10a and 10g exhibited Ki values of 23.2, 19.4, and 43.2 nM against OfChi-h, respectively. Molecular docking studies were carried out to explore the molecular basis for the high efficacy of these compounds and OfChi-h. In addition, the morphological changes of the cuticle in inhibitor-treated O. furnacalis larvae were assessed using scanning electron microscopy. Furthermore, the target compounds were assayed in leaf dipping and pot experiments, with compound 10a exhibiting greater insecticidal activity against Plutella xylostella (P. xylostella) and O. furnacalis than diflubenzuron and chlorbenzuron. At the same time, the toxicity of these compounds to natural enemies Trichogramma ostriniae and rats was negligible. The present study demonstrates that the azo-aminopyrimidine skeleton can be used as a novel, low-cost scaffold for developing insect chitinolytic enzyme inhibitors, with the potential to be utilized as new environmentally friendly insecticides.
期刊介绍:
Plant Biotechnology Journal aspires to publish original research and insightful reviews of high impact, authored by prominent researchers in applied plant science. The journal places a special emphasis on molecular plant sciences and their practical applications through plant biotechnology. Our goal is to establish a platform for showcasing significant advances in the field, encompassing curiosity-driven studies with potential applications, strategic research in plant biotechnology, scientific analysis of crucial issues for the beneficial utilization of plant sciences, and assessments of the performance of plant biotechnology products in practical applications.