State Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China.
College of Basic Science, Tianjin Agricultural University, Tianjin 300384, China.
J Agric Food Chem. 2023 Jul 26;71(29):11016-11025. doi: 10.1021/acs.jafc.3c02480. Epub 2023 Jul 13.
Marine natural products have attracted more and more attention in drug research and development due to their unique structure, diverse biological activities, and novel mode of action. Using antiviral alkaloid aldisine as the lead compound and drawing on the hydrogen bond effect widely used in drug design, derivatives containing oxime and hydrazone moieties were designed and synthesized by introducing functional groups with hydrogen-bond receptors or donors into molecules. The configuration of derivatives was systematically studied through nuclear Overhauser effect (NOE) spectroscopy and single crystal analysis. The antiviral activity test result showed that most derivatives had antiviral activity against tobacco mosaic virus (TMV), and some compounds had better activity than the commercial antiviral drug ribavirin, especially compounds and , which had comparable activity to the most effective commercial antiviral drug ningnanmycin. Preliminary mode of action studies showed that compound could affect the assembly of rod-shaped TMVs by promoting the aggregation and fragmentation of TMV coat proteins. Molecular docking experiments demonstrated that the introduction of oxime and hydrazone moieties could indeed increase the hydrogen bond between molecules and target proteins. In addition, we conducted fungicidal and larvicidal activities study of these derivatives. Most of these derivatives had good larvicidal activities against and and showed broad-spectrum fungicidal activities.
海洋天然产物由于其独特的结构、多样的生物活性和新颖的作用模式，在药物研发中越来越受到关注。以抗病毒生物碱阿迪斯碱为先导化合物，借鉴药物设计中广泛应用的氢键效应，通过在分子中引入氢键受体或供体的官能团，设计并合成了含有肟和腙部分的衍生物。通过核奥弗豪瑟效应（NOE）光谱和单晶分析系统地研究了衍生物的构型。抗病毒活性测试结果表明，大多数衍生物对烟草花叶病毒（TMV）具有抗病毒活性，一些化合物的活性优于商业抗病毒药物利巴韦林，特别是化合物 和 ，其活性与最有效的商业抗病毒药物宁南霉素相当。初步作用模式研究表明，化合物 可以通过促进 TMV 外壳蛋白的聚集和碎片化来影响棒状 TMV 的组装。分子对接实验表明，肟和腙部分的引入确实可以增加分子与靶蛋白之间的氢键。此外，我们还对这些衍生物进行了杀菌和杀虫活性研究。大多数衍生物对 和 具有良好的杀虫活性，表现出广谱杀菌活性。
