College of Plant Protection, Northwest A&F University, 3 Taicheng Road, Yangling ,Shaanxi 712100, China.
College of Chemistry & Pharmacy, Northwest A&F University, 22 Xinong Road, Yangling, Shaanxi 712100, China.
J Agric Food Chem. 2022 Aug 24;70(33):10316-10325. doi: 10.1021/acs.jafc.2c03632. Epub 2022 Aug 12.
On the basis of the structure of nicotlactone A (), a series of novel α-methylene-γ-butyrolactone derivatives were designed and synthesized by structure simplification and active fragment replacement strategies, and their antiviral and antifungal activities were evaluated. The bioassay studies indicated that many target compounds possessed good to excellent antiviral activity against tobacco mosaic virus (TMV) and some of these compounds exhibited specific antifungal activities against and . Compound exhibited the best anti-TMV activity (inactivation effect, 88.9%; protection effect, 65.8%; curative effect, 52.8%) at 500 mg/L, which is significantly higher than that of commercial virucides ribavirin and ningnanmycin. The inhibition effect of compound was also visualized by the inoculation test using green fluorescent protein (GFP)-labeled TMV. The preliminary antiviral mechanism of compound was investigated. Transmission electron microscopy (TEM) showed that compound could destroy the integrity of virus particles. Then, molecular docking and isothermal titration calorimetry (ITC) analysis further demonstrated that compound exhibited a strong binding affinity to the TMV coat protein with a dissociation constant () of 3.06 μM, superior to ribavirin. Thus, we deduced that compound may interfere with the self-assembly of TMV particles by binding TMV coat protein (CP). In addition, compound showed good activity against with an inhibition rate of 90.9% at 50 mg/L, which was greater than that of fluxapyroxad (59.1%) but lower than that of the commercial fungicide carbendazim (96.8%). The present study provides support for the application of these α-methylene-γ-butyrolactone derivatives as novel antiviral and antifungal agents in crop protection.
基于烟碱内酯 A（）的结构，通过结构简化和活性片段替换策略，设计并合成了一系列新型的α-亚甲基-γ-丁内酯衍生物，并评价了它们的抗病毒和抗真菌活性。生物测定研究表明，许多目标化合物对烟草花叶病毒（TMV）具有良好到优异的抗病毒活性，其中一些化合物对和表现出特定的抗真菌活性。化合物在 500mg/L 时表现出最好的抗 TMV 活性（失活作用，88.9%；保护作用，65.8%；治疗作用，52.8%），显著高于商业病毒抑制剂利巴韦林和宁南霉素。化合物的抑制作用也可以通过用绿色荧光蛋白（GFP）标记的 TMV 接种试验来观察到。初步研究了化合物的抗病毒机制。透射电子显微镜（TEM）显示，化合物可以破坏病毒颗粒的完整性。然后，分子对接和等温滴定量热法（ITC）分析进一步表明，化合物与 TMV 外壳蛋白具有很强的结合亲和力，解离常数（）为 3.06μM，优于利巴韦林。因此，我们推断化合物可能通过与 TMV 外壳蛋白（CP）结合来干扰 TMV 颗粒的自组装。此外，化合物在 50mg/L 时对表现出良好的活性，抑制率为 90.9%，高于氟吡菌酰胺（59.1%），但低于商业杀菌剂多菌灵（96.8%）。本研究为这些α-亚甲基-γ-丁内酯衍生物作为新型抗病毒和抗真菌剂在作物保护中的应用提供了支持。
