RESUMO
The hypolipidemic effect of furan carboxamide derivatives was investigated using the Triton WR-1339 rat model. Nineteen compounds were synthesized, including furan-2-carboxamides of benzophenones and acetophenones (a(1-4)), anilines and amine derivatives (a(5-9)), picolinic-2-carboxamide derivatives of benzophenones and acetophenone (a(10-12)) and furan-2-carboxylate esters of benzophenones and acetophenones, substituted phenols and alcohols (b(1-7)). All the necessary steps were taken to synthesize, purify, and characterize these compounds. They were synthesized by reacting acyl chlorides of the heterocycles with their corresponding amines in the presence of pyridine and tert-butyl acetate. While the conventional heating method yielded acceptable yields for some of the reactions under reflux, the microwave synthesis reactor achieved significantly higher yields for others. Rats with hyperlipidemia were induced with Triton WR-1339 and then subjected to in vivo testing via an intraperitoneal injection of 200 mg kg-1 Triton WR-1339. The model was tested using an oral dose of bezafibrate (100 mg kg-1). After 7 hours of treatment with Triton, the new derivatives represented by compounds a(1-2), a(4-5), a7, and a(10-12) showed significant activity against the complete lipid profile, including a decrease in triglyceride, total cholesterol, and low-density lipoprotein cholesterol and an increase in high-density lipoprotein cholesterol plasma levels. At 20 mg kg-1 dose, these compounds were superior to other lipid-lowering agents in reducing triglyceride levels and slightly increased high-density lipoprotein cholesterol levels. These results indicate a mutual mechanism of action of novel compounds with fibrates, where they have a marked effect on triglyceride and high-density lipoprotein cholesterol levels; for example, a5 causes a significant reduction (p 0.0001) of triglyceride levels by 86%, and a remarkable increase (p 0.0001) in high-density lipoprotein cholesterol plasma levels by 65% as compared to hyperlipidemic rats.
RESUMO
Diabetes mellitus is a predominant cause of mortality and morbidity worldwide. One of its serious health problems is cardiovascular complications. Advanced glycation end products (AGEs) are a group of heterogeneous toxic oxidant compounds that are formed after a non-enzymatic reaction between monosaccharides and free amino groups of proteins, compound lipids, and nucleic acids. AGE interacts with various types of cells through a receptor for AGE (RAGE). The interaction between AGE and RAGE is responsible for a cascade of inflammation, oxidative stress, and disruption of calcium homeostasis in cardiac cells of diabetic patients. There is striking evidence that the AGE/RAGE axis with its consequences on inflammation and oxidative stress plays a major role in the development of cardiovascular complications. Therefore, considering AGE as a therapeutic target with foreseeable results would be a wise direction for future research. Interestingly, several studies on nutraceutical, pharmaceutical, and natural products have begun to reveal promising therapeutic results, and this could lead to better health outcomes for many diabetic patients worldwide. This article discusses the current literature addressing the connection between protein glycation and diabetes cardiovascular complications and suggests future avenues of research.
