Synthesis and Biological Evaluation of Novel Bouchardatine Derivatives as Potential Adipogenesis/Lipogenesis Inhibitors for Antiobesity Treatment
Synthesis and Biological Evaluation of Novel Bouchardatine Derivatives as Potential Adipogenesis/Lipogenesis Inhibitors for Antiobesity Treatment
复制标题
作为抗肥胖治疗的潜在脂肪生成/脂肪生成抑制剂的新型 Bouchardatine 衍生物的合成和生物学评价。
DOI：
10.1021/acs.jmedchem.5b01566
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发表时间：
2015-12-10
影响因子：
7.3
通讯作者：
Huang, Zhi-Shu
中科院分区：
文献类型：
--
作者：
Rao, Yong;Liu, Hong;Huang, Zhi-Shu
Our recent study has shown that the natural product bouchardatine (1) can reduce the triglyceride (TG) content in 3T3-L1 adipocytes (EC50 approximate to 25 mu M). Here, we synthesized two series of compounds by introducing amine side chains at the 5 or 8 position of 1 and evaluated the lipid-lowering activity of derivatives. It was found that some of the compounds had significant lipid-lowering effects, and the most active compound 3d showed better activity (EC50 = 0.017 mu M) than 2 (EC50 = 0.086 mu M), a compound reported by us. Further, the mechanism studies revealed that 3d blocked TG accumulation via activation of the LKB1-AMPK signaling pathway, efficiently down-regulating the expression of key regulators of adipogenesis/lipogenesis. Cell uptake assay and confocal imaging of 3d in cells indicated that compound 3d had favorable cell permeability. Our results suggest that 3d may be a promising agent for the treatment of obesity and related metabolic disorders.
