Synthesis and in vivo anti-hyperlipidemic activity of novel n-benzoylphenyl-2-furamide derivatives in Wistar rats

Purpose: To synthesize and evaluate the anti-hyperlipidemic activity of a novel series of N-(benzoylphenyl)-2-furamides (3a, 3b, 4a, 4b and 4c).
Methods: Compounds (3a, 3b, 4a, 4b and 4c) were successfully synthesized by reacting activated furan-2-carbonyl-chloride derivatives with aminobenzophenones at 60 °C for 36 h. Hyperlipidemia was induced in overnight fasted rats by intraperitoneal administration of Triton WR-1339 (300 mg/kg). to overnight fasted rats. The rats were divided into six groups: control, hyperlipidemic, hyperlipidemic plus compounds 3b, 4b, 4c, and hyperlipidemic plus bezafibrate-treated. Eighteen hours later, blood samples were collected and plasma lipid profile determined using enzymatic methods.
Results: At a dose of 15 mg/kg body weight, the elevated plasma triglyceride (TG) levels, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels were significantly reduced by compounds 4b (p < 0.001) and 4c (p < 0.0001) 18 h later, compared to the hyperlipidemic group. Furthermore, compounds 4b and 4c significantly increased high density lipoprotein cholesterol (HDL-C) levels by 29 and 34 %, respectively.
Conclusion: The findings indicate the high potency of N-(benzolphenyl)-2-furamides (4b and 4c) as lipid-lowering agents. Thus, these compounds 4b and 4c may used as lead compounds for the development of new derivatives and agents for targeting dyslipidemia and cardiovascular diseases.

Keywords
Triton WR-1339-induced hyperlipidemic rats; N-(benzoylphenyl)-2-furamides; Lipid-lowering activity; Cardiovascular disease; Synthesis