炎症是对刺激的复杂生物学反应。活化的巨噬细胞诱导过度释放促炎性细胞因子，而内源性自由基一氧化氮（NO）等介体在多种炎性疾病的进展中起重要作用。天然和合成查耳酮都具有广泛的生物活性。在这项工作中，基于生物活性卡瓦尔查耳酮，设计，合成了39个查耳酮和3种相关化合物，包括几种新化合物，并评估了它们对RAW 264.7细胞中NO产生的抑制作用。新型化合物（E）-1-（2'-羟基-4'，6'-二甲氧基苯基）-3-（3-甲氧基-4-（3-吗啉代丙氧基）苯基）丙-2-烯-1-酮（53）对10μM（IC的NO产生）表现出更好的抑制活性（84.0％）50  = 6.4μM）的细胞毒性（IC 50  > 80μM）在测试化合物中最低。此外，蛋白质印迹分析表明化合物53是诱导型一氧化氮合酶（iNOS）蛋白的有效下调剂。对接研究表明，化合物53也可以对接iNOS的活性位点。此外，在剂量为10 mg / kg / day时，化合物53均可显着抑制胶原蛋白诱导的关节炎（CIA）和佐剂诱导的关节炎（AIA）模型上的炎症进展。另外，还描绘了基于卡瓦查耳酮的类似物的结构-活性关系（SAR）。

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Inflammation is a complex biological response to stimuli. Activated macrophages induced excessively release of pro-inflammatory cytokines and mediators such as endogenous radical nitric oxide (NO) play a significant role in the progression of multiple inflammatory diseases. Both natural and synthetic chalcones possess a wide range of bioactivities. In this work, thirty-nine chalcones and three related compounds, including several novel ones, based on bioactive kava chalcones were designed, synthesized and their inhibitory effects on NO production in RAW 264.7 cells were evaluated. The novel compound (E)-1-(2′-hydroxy-4′,6′-dimethoxyphenyl)-3-(3-methoxy-4-(3-morpholinopropoxy)phenyl)prop-2-en-1-one (53) exhibited a better inhibitory activity (84.0%) on NO production at 10 μM (IC50 = 6.4 μM) with the lowest cytotoxicity (IC50 > 80 μM) among the tested compounds. Besides, western blot analysis indicated that compound 53 was a potent down-regulator of inducible nitric oxide synthase (iNOS) protein. Docking study revealed that compound 53 also can dock into the active site of iNOS. Furthermore, at the dose of 10 mg/kg/day, compound 53 could both significantly suppress the progression of inflammation on collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) models. In addition, the structure-activity relationship (SAR) of the kava chalcones based analogs was also depicted.