Design, synthesis and evaluation of 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-Based fibrates as potential hypolipidemic and hepatoprotective agents.

Abstract

Six novel target compounds 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT) based fibrates were synthesized and evaluated. All the synthesized compounds were preliminarily screened by using the Triton WR-1339-induecd hyperlipidemia model, in which T1 exhibited more potent hypolipidemic property than positive drug fenofibrate (FF). T1 also significantly decreased serum triglycerides (TG), total cholesterol (TC) and low density lipoprotein cholesterin (LDL) in methionine solution (Mets) induced hyperlipidemic mice. Moreover, hepatic transaminases (AST and ALT) were obviously ameliorated after treatment with T1 and the histological observation indicated that T1 ameliorated the injury in liver tissue and inhibited the hepatic lipid accumulation. In the livers of T1-administrated rat, the levels of PPARα related to lipids metabolism were up-regulated. Additional effects such as antioxidant, anti-inflammatory and H2S releasing action confirmed and reinforced the activity of T1 as a potential multifunctional hypolipidemic and hepatoprotective agent.

• Authors: Lihua Shao, Yue Bai, Qiutang Wang, Zizhang Chen, Yundong Xie, Xiaoli Bian
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 29 Issue 23 Pg. 126723 (12 01 2019) ISSN: 1464-3405 [Electronic] England
• PMID: 31624042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Fibric Acids
• Hypolipidemic Agents

Topics

• Animals
• Fibric Acids (chemical synthesis, chemistry)
• Hypolipidemic Agents (pharmacology, therapeutic use)
• Lipid Metabolism (drug effects)
• Male
• Mice
• Rats