College of Pharmacy, Shaanxi University of Chinese Medicine, Xi'an-xianyang New Ecomic Zone 712046, China.
The People's Hospital of Yongcheng, 888 Ouya Road, Yongcheng City, Shangqiu City, Henan Province 476600, China.
Bioorg Med Chem Lett. 2021 Jul 1;43:127898. doi: 10.1016/j.bmcl.2021.127898. Epub 2021 Mar 6.
A series of target compounds 1,3-benzodioxole-based fibrate derivatives were designed and synthesized. All the target compounds were preliminarily evaluated by hyperlipidemia mice induced by Triton WR-1339, in which compound 12 displayed a greater anti-hyperlipidemia activity than other compounds as well as positive drug fenofibrate (FF). 12 showed a significant reduction of plasma lipids, such as triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterin (LDL-C), in high fat diet (HFD) induced hyperlipidemic mice. In addition, hepatic transaminases (AST and ALT) were ameliorated after administration of 12, in particular the AST, and the histopathological examination showed that 12 improved the hepatic lipid accumulation. The expression of PPAR-α involved in lipids metabolism was up-regulated in the liver tissues of 12-treated group. Other significant activity such as antioxidant, and anti-inflammation was confirmed and reinforced the effects of 12 as a potential hypolipidemia and hepatoprotective agent.
设计并合成了一系列基于 1,3-苯并二恶唑的纤维酸酯衍生物的目标化合物。所有目标化合物均通过 Triton WR-1339 诱导的高脂血症小鼠进行了初步评估，其中化合物 12 的抗高血脂活性优于其他化合物以及阳性药物非诺贝特（FF）。12 可显著降低高脂饮食（HFD）诱导的高脂血症小鼠的血浆脂质，如甘油三酯（TG）、总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）。此外，12 可改善肝转氨酶（AST 和 ALT），特别是 AST，组织病理学检查表明 12 可改善肝脏脂质堆积。参与脂质代谢的 PPAR-α 在 12 处理组的肝脏组织中上调。其他重要的活性，如抗氧化和抗炎，也得到了证实，并加强了 12 作为一种潜在的降血脂和保肝剂的作用。
