Excess lipid accumulation in the arterial intima and formation of macrophage-derived foam cells in the plaque could cause atherosclerotic lesion. Cholesterol absorption inhibitors could suppress the lipid accumulation of human macrophage, inflammatory response and the development of atherosclerosis. In this research, a series of 1H-pyrrole-2,5-dione derivatives were synthesized as cholesterol absorption inhibitor and tested in in vitro experiments. One of the most active inhibitors, compound 20 exhibited stronger in vitro cholesterol absorption activity than ezetimibe, no cytotoxicity in HEK293 and RAW264.7 cell lines and satisfied lipophilicity. The further study indicated that 20 could inhibit lipid accumulation of macrophage and reduce the secretion of LDH, MDA, TNF-α and ROS in a concentration-dependent manner. In conclusion, as a novel and potent cholesterol absorption inhibitor, compound 20 could suppress the formation of foam cells and inflammatory response.

动脉内膜中过多的脂质蓄积和斑块中巨噬细胞衍生的泡沫细胞的形成可能导致动脉粥样硬化病变。胆固醇吸收抑制剂可以抑制人巨噬细胞的脂质蓄积，炎症反应和动脉粥样硬化的发展。在这项研究中，合成了一系列1 H-吡咯-2,5-二酮衍生物作为胆固醇吸收抑制剂，并在体外实验中进行了测试。一个最活跃的抑制剂，化合物20表现出强的体外比的依折麦布胆固醇吸收活性，在HEK293和RAW264.7细胞系和亲油性满意无细胞毒性。进一步的研究表明20可以抑制巨噬细胞脂质的积累，并以浓度依赖的方式减少LDH，MDA，TNF-α和ROS的分泌。总之，化合物20作为一种新型有效的胆固醇吸收抑制剂，可以抑制泡沫细胞的形成和炎症反应。