Xu Wentao, Yang Kangkang, Li Mingxing, Li Longqi, Xing Fuqiao, Li Jiayi, Liu Yuxiu, Zhang Jingjing, Wang Qingmin, Song Hongjian
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.
Int J Mol Sci. 2025 Aug 27;26(17):8308. doi: 10.3390/ijms26178308.
Marine natural products have gained increasing interest in drug research and development because of their unique structures, diverse biological activities, and novel mechanisms of action. Using the antiviral alkaloid aldisine as the lead compound and utilizing the hydrogen bond effects common in drug design, novel derivatives containing an acylhydrazone moiety were designed and synthesized. The structures of these derivatives were systematically analyzed using variable-temperature H-NMR. Antiviral activity tests showed that most derivatives were active against tobacco mosaic virus (TMV), with some compounds outperforming the commercial antiviral drug ribavirin. Notably, 3-methylphenyl- and 3-pyridyl-substituted acylhydrazones and displayed activity comparable to ningnanmycin, one of the most effective commercial antiviral agents. Molecular docking results indicated that incorporating the acylhydrazone moiety enhances hydrogen bonding between the molecules and target proteins. Additionally, we evaluated the fungicidal and larvicidal activities of these derivatives. Most exhibited significant larvicidal effects against and , along with broad-spectrum fungicidal activity. Four related compounds (, , , and ) exhibited high fungicidal activities, and another four compounds (, , , and ) exhibited high larvicidal activities.
海洋天然产物因其独特的结构、多样的生物活性和新颖的作用机制，在药物研发中越来越受到关注。以抗病毒生物碱阿尔迪辛为先导化合物，并利用药物设计中常见的氢键效应，设计并合成了含酰腙部分的新型衍生物。使用变温氢核磁共振对这些衍生物的结构进行了系统分析。抗病毒活性测试表明，大多数衍生物对烟草花叶病毒（TMV）具有活性，一些化合物的表现优于商业抗病毒药物利巴韦林。值得注意的是，3-甲基苯基和3-吡啶基取代的酰腙显示出与最有效的商业抗病毒剂之一宁南霉素相当的活性。分子对接结果表明，引入酰腙部分增强了分子与靶蛋白之间的氢键作用。此外，我们评估了这些衍生物的杀真菌和杀幼虫活性。大多数对和表现出显著的杀幼虫作用，同时具有广谱杀真菌活性。四种相关化合物（、、、和）表现出高杀真菌活性，另外四种化合物（、、、和）表现出高杀幼虫活性。
