痛风是仅次于糖尿病的全球第二大代谢性疾病，其中急性痛风性关节炎是最常见的症状。黄嘌呤氧化酶 (XOD) 和 NOD 样受体 3 (NLRP3) 炎性体是急性痛风治疗的关键靶点。据报道，绿原酸具有良好的抗炎活性，芹菜素在 XOD 抑制方面表现出优异的潜力。因此，设计并合成了一系列具有不同接头的绿原酸-芹菜素（CA）缀合物作为XOD/NLRP3双重抑制剂，并评估了它们在XOD和NLRP3抑制方面的活性。 XOD 抑制活性的体外研究表明，大多数 CA 缀合物表现出良好的 XOD 抑制活性。特别地，在芹菜素部分上具有烷基连接基的化合物10c和10d的作用比别嘌呤醇更强。所选的 CA 缀合物还在 RAW264.7 细胞中表现出良好的抗炎活性。此外，选择在XOD抑制和抗炎方面均表现出最佳活性的化合物10d，并进一步测试其对NLRP3和相关促炎细胞因子的抑制能力。化合物10d有效降低NLRP3表达以及白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的分泌，其活性强于阳性对照异甘草素(ISL)。基于这些发现，化合物10d表现出双重XOD/NLRP3抑制活性，因此，其对急性痛风的治疗作用值得进一步研究。

Gout is the second largest metabolic disease worldwide after diabetes, with acute gouty arthritis as most common symptom. Xanthine oxidase (XOD) and the NOD like receptor-3 (NLRP3) inflammasome are the key targets for acute gout treatment. Chlorogenic acid has been reported with a good anti-inflammatory activity, and Apigenin showed an excellent potential in XOD inhibition. Therefore, a series of chlorogenic acid-apigenin (CA) conjugates with varying linkers were designed and synthesized as dual XOD/NLRP3 inhibitors, and their activities both in XOD and NLRP3 inhibition were evaluated. An in vitro study of XOD inhibitory activity revealed that the majority of CA conjugates exhibited favorable XOD inhibitory activity. Particularly, the effects of compounds 10c and 10d, with an alkyl linker on the apigenin moiety, were stronger than that of allopurinol. The selected CA conjugates also demonstrated a favorable anti-inflammatory activity in RAW264.7 cells. Furthermore, compound 10d, which showed the optimal activity both in XOD inhibition and anti-inflammatory, was chosen and its inhibitory ability on NLRP3 and related proinflammatory cytokines was further tested. Compound 10d effectively reduced NLRP3 expression and the secretion of interluekin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) with an activity stronger than the positive control isoliquiritigenin (ISL). Based on these findings, compound 10d exhibits dual XOD/NLRP3 inhibitory activity and, therefore, the therapeutic effects on acute gout is worthy of further study.