Substituted furan-carboxamide and Schiff base derivatives as potential hypolipidemic compounds: evaluation in Triton WR-1339 hyperlipidemic rat model

Substituted furan carboxamide and Schiff base derivatives were evaluated for their hypolipidemic activity. Fourteen derivatives were synthesised: substituted-furan-2-carboxamides of acetophenones, anilines, and benzophenones a (1–8), furan-3-carboxamide (c1), and imines derivatives b (1–5). These compounds were synthesised, purified and fully characterised. All the new derivatives were verified in-vivo utilising Triton WR-1339 induced hyperlipidemic rats as animal model. The potential agents were administered via intraperitoneal injection of 20 mg/kg. Fenofibrate (with a dose 100 mg/kg, orally) was used in this research to validate the model. Remarkably, the new derivatives a (1–8), b (1–5) and c1 have shown significant effect against the whole lipid profile; by lowering the plasma triglyceride (TG), plasma total cholesterol (TC), low-density lipoprotein (LDL) level and elevating high-density lipoproteins (HDL) plasma levels comparing to the hyperlipidemic rats. The agents reduce TG with most significant results by (97%, 96%, 87% and 86%) relating to a1, a3, a8 and b5 respectively. Favourably, some of the proposed agents are more significant in reducing TG than fenofibrate. Some agents reduce LDL with most significant results by (76%, 72%, 60%, 60% and 60%) relating to a1, a3, a5, a8 and b5 respectively, and to a lower extent they increase HDL levels with most significant results by (75%, 64%, and 48%) for a1, a3, and a5 respectively. All the new derivatives were computationally docked at the hPPAR-α active site as possible target for these derivatives. The binding affinities were reported and showed good correlation to the in-vivo results as antihyperlipidemic agents.