A series of cytosine derivatives containing a sulfonamide moiety were designed and synthesized, and their antiviral activities against pepper mild mottle virus (PMMoV) were systematically evaluated. Then, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was constructed to study the structure-activity relationship according to the pEC₅₀ of the compounds’ protective activities. Next, compound A32 with preferable antiviral activity on PMMoV was obtained based on the CoMSIA and CoMFA models, with an EC₅₀ of 19.5 μg/mL, which was superior to the template molecule A25 (21.3 μg/mL) and ningnanmycin (214.0 μg/mL). In addition, further studies showed that the antiviral activity of compound A32 against PMMoV was in accord with the up-regulation of proteins expressed in the defense response and carbon fixation in photosynthetic organisms. These results indicated that cytosine derivatives containing a sulfonamide moiety could be used as novel potential antiviral agents for further research and development.

中文翻译：

---

首次发现含有磺胺部分的新型胞嘧啶衍生物作为潜在的抗病毒剂

设计并合成了一系列含有磺胺部分的胞嘧啶衍生物，并系统评价了它们对辣椒轻度斑驳病毒（PMMoV）的抗病毒活性。然后，构建三维定量构效关系（3D-QSAR）模型，根据化合物保护活性的pEC _{50研究构效关系。}接着，基于CoMSIA和CoMFA模型获得了对PMMoV具有较好抗病毒活性的化合物A32 ，其EC ₅₀为19.5 μg/mL，优于模板分子A25（21.3 μg/mL）和宁南霉素（214.0 μg/毫升）。此外，进一步的研究表明，化合物A32的抗病毒活性抗 PMMoV 与光合生物防御反应和碳固定中表达的蛋白质的上调一致。这些结果表明，含有磺胺部分的胞嘧啶衍生物可用作新的潜在抗病毒剂，用于进一步的研究和开发。