Details

Autor(en) / Beteiligte

• Liu, Yu-Chen
• Wei, Gang
• Liao, Zhi-Qiang
• Wang, Fang-Xin
• Zong, Chunxiao
• Qiu, Jiannan
• Le, Yifei
• Yu, Zhi-Ling
• Yang, Seo Young
• Wang, Heng-Shan
• Dou, Xiao-Bing
• Wang, Cai-Yi

Titel

Design and Synthesis of Novel Indole Ethylamine Derivatives as a Lipid Metabolism Regulator Targeting PPARα/CPT1 in AML12 Cells

Ist Teil von

• Molecules (Basel, Switzerland), 2023-12, Vol.29 (1), p.12

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2023

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 ( , , , ) were designed and synthesized. The target product (compound ) 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 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 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 lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy.