白藜芦醇骨架是一种有前途的化学支架，具有抗炎、抗抑郁和抗肿瘤效果。在本研究中，我们旨在降低化合物32（初步工作）在体内和体外的毒性，并保持其生物活性。设计并合成了一系列新型白藜芦醇衍生物（D1-D43），并对其抗炎活性进行了筛选。所有化合物都进行了筛选，以评估它们对LPS / Nigericin诱导的IL-1β产生和焦亡的抑制作用。推导了结构活性关系，最终发现1-（（E）-4-（2-乙氧基乙氧基）苯乙烯基）-3,5-二甲氧基-2-（（E）-2-硝基乙烯基）苯（D22）是一种低毒性化合物，具有最有效的抑制效果（抗IL-1β：IC50 = 2.41μM）。初步的机制研究表明，化合物D22可能通过靶向NLRP3蛋白影响NLRP3炎症小体的组装，从而抑制NLRP3炎症小体的活化。体内抗炎活性表明，化合物D22对DSS诱导的小鼠急性结肠炎模型有显著的治疗效果。版权所有©2023 Elsevier Inc. 保留所有权利。

The pterostilbene skeleton is a promising chemical scaffold that exerts anti-inflammatory, anti-depressant, and anti-tumor effects. In this study, we aim to reduce in vivo and in vitro toxicity of compound 32 (preliminary work) and maintain its biological activity. A series of novel pterostilbene derivatives (D1-D43) were designed and synthesized, and their anti-inflammatory activities were screened. All compounds were screened to evaluate their inhibitory effect on LPS/Nigericin-induced IL-1β production and pyroptosis. The structure-activity relationships was deduced, and finally 1-((E)-4-(2-ethoxyethoxy)styryl)-3,5-dimethoxy-2-((E)-2-nitrovinyl)benzene (D22) was found to be a low-toxic compound with most potent inhibitory efficacy (against IL-1β: IC50 = 2.41 μM). Preliminary mechanism studies showed that compound D22 may affect the assembly of NLRP3 inflammasome by targeting NLRP3 protein, thereby inhibiting the activation of NLRP3 inflammasome. The in vivo anti-inflammatory activity indicated that compound D22 had significant therapeutic effects on DSS-induced mouse acute colitis models.Copyright © 2023 Elsevier Inc. All rights reserved.