First Discovery of Novel Cytosine Derivatives Containing a Sulfonamide Moiety as Potential Antiviral Agents

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.

一系列含有磺酰胺基团的胞嘧啶衍生物被设计并合成，其针对辣椒花叶病毒（PMMoV）的抗病毒活性被系统性地评估。随后，基于化合物的保护活性pEC50，构建了三维定量构效关系（3D-QSAR）模型，以研究其构效关系。接着，依据CoMSIA和CoMFA模型，获得了一种具有优良PMMoV抗病毒活性的化合物A32，其EC50值为19.5 μg/mL，优于模板分子A25（21.3 μg/mL）和宁南霉素（214.0 μg/mL）。此外，进一步的研究表明，化合物A32对PMMoV的抗病毒活性与光合生物防御响应和碳固定的蛋白质表达上调相一致。这些结果指出，含有磺酰胺基团的胞嘧啶衍生物可作为新型潜在抗病毒剂，为进一步的研究和开发提供可能。