Molecules, Vol. 29, Pages 12: Design and Synthesis of Novel Indole Ethylamine Derivatives as a Lipid Metabolism Regulator Targeting PPAR & alpha;/CPT1 in AML12 Cells

Molecules, Vol. 29, Pages 12: Design and Synthesis of Novel Indole Ethylamine Derivatives as a Lipid Metabolism Regulator Targeting PPARα/CPT1 in AML12 Cells Molecules doi: 10.3390/molecules29010012 Authors: Yu-Chen Liu Gang Wei Zhi-Qiang Liao Fang-Xin Wang Chunxiao Zong Jiannan Qiu Yifei Le Zhi-Ling Yu Seo Young Yang Heng-Shan Wang Xiao-Bing Dou Cai-Yi Wang Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) therapy. In the present study, a set of novel indole ethylamine derivatives (4, 5, 8, 9) were designed and synthesized. The target product (compound 9) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 μM of compound 9 reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound 9 supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipoge...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research