In order to identify a suitable alternative to non-steroidal anti-inflammatory drugs (NSAIDs) we aimed to develop derivatives of vortioxetine, a multimodal anti-depressive drug that has been shownpreviously to be endowed withanti-inflammatory activity in human monocytes/macrophages. Vortioxetine (1) was synthesized in good yield and different alkyl and aryl derivatives were prepared based on their structural diversity and easy availability. The compounds were tested on human monocytes isolated from healthy donors for theireffect on superoxide anion production and cytokine gene expression, and for COX-1/2 gene expression and activity modulation. Moreover, a docking study was performed to predict the interactions between the synthesized compounds and COX-1 and COX-2. Correlating experimental biological data to the molecular modelling studies, it emerged that among the novel compounds, 6 was endowed of antioxidant and anti-COX-1 activity, vortioxetine and 3 were good antioxidants and mild anti-COX-1/2 inhibitors, while 7 was a good anti-COX-1/2 inhibitor and 11 was more specific versus COX-2.

为了确定非甾体抗炎药（NSAIDs）的合适替代品，我们旨在开发伏替西汀的衍生物，该药物是一种多模态抗抑郁药，先前已被证明具有人类单核细胞/巨噬细胞的抗炎活性。伏替西汀（1）以高收率合成，并根据其结构多样性和易获得性制备了不同的烷基和芳基衍生物。在从健康供体分离的人单核细胞上测试了这些化合物对超氧阴离子产生和细胞因子基因表达的影响，以及对COX-1 / 2基因表达和活性调节的影响。此外，进行了对接研究以预测合成的化合物与COX-1和COX-2之间的相互作用。将实验生物学数据与分子模型研究相关联，发现在这些新化合物中，有6种具有抗氧化剂和抗COX-1活性，伏替西汀和3种是良好的抗氧化剂和温和的抗COX-1 / 2抑制剂，而7种是是一种良好的抗COX-1 / 2抑制剂，并且11种的特异性高于COX-2。