5-(4-Hydroxyphenyl)-3H-1,2-dithiole-3-thione-based fibrates as potential hypolipidemic and hepatoprotective agents

• Published in: Bioorganic & medicinal chemistry letters 2018-12, Vol.28 (23-24), p.3787-3792
• Main Authors: Chen, Zi-Zhang, Xie, Yun-Dong, Shao, Li-Hua, Wang, Qiu-Tang, Xu, Yan-Hong, Bian, Xiao-Li
• Format: Article
• Language: English
• Subjects: Animals; Diet, High-Fat - adverse effects; Fibrates; Fibric Acids - chemistry; Fibric Acids - pharmacology; Fibric Acids - therapeutic use; Hepatoprotection; Hyperlipidemias - blood; Hyperlipidemias - drug therapy; Hyperlipidemias - etiology; Hyperlipidemias - metabolism; Hypolipidemic; Hypolipidemic Agents - chemistry; Hypolipidemic Agents - pharmacology; Hypolipidemic Agents - therapeutic use; Lipid Metabolism - drug effects; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Mice; Protective Agents - chemistry; Protective Agents - pharmacology; Protective Agents - therapeutic use; Thiones - chemistry; Thiones - pharmacology; Thiones - therapeutic use; Thiophenes - chemistry; Thiophenes - pharmacology; Thiophenes - therapeutic use
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.10.003

[Display omitted] •Design of 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione derivatives with a significantly hypolipidemic activity.•Study indicated that tested compound also showed hepatoprotective activity in hyperlipidaemia.•The tested compound displayed potent antioxidant and anti-inflammatory activities. Hypolipidemic effects of the newly synthesized 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-based fibrates were evaluated in Triton WR-1339 and high-fat diet (HFD)-induced hyperlipidemic mice. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton WR-1339 model), in which compound 6 shown more significant antidyslipidemic activity than fenofibrate (FF). The compound 6 was also found to reduce serum triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterin (LDL) in HFD-induced hyperlipidemic mice. Moreover, compound 6 displayed hepatoprotective effect, a significant amelioration in hepatic indices (AST and ALT) toxicity was observed and the histological examination showed that compound 6 inhibited the development of hepatic lipid accumulation and ameliorated the damage in hepatic tissue compared to model mice. Additional effects such as the potent antioxidant and anti-inflammatory action confirmed and reinforced the efficacy of compound 6 as a new agent of dual-effect hypolipidemic and hepatoprotective activities.