Abstract
Hyperlipidemia, marked by high levels of fats in the blood, is a major risk factor for non-communicable diseases such as type 2 diabetes, cardiovascular diseases, and cancer. It has been linked to the action of reactive oxygen species and the formation of advanced glycation end products. Current treatments for hyperlipidemia, like orlistat, simvastatin, and atorvastatin, often present undesirable side effects, prompting the need for new therapeutic agents that are safer, more effective, cost-efficient, and have fewer side effects. In this context, new compounds, specifically propano- and butanosulfonic acids with 9-substituted quinobenzothiazinyl substituents, were synthesized through reactions with 9-substituted quinobenzothiazines and propane sultone or butane sultone. These novel quinobenzothiazine derivatives were verified using (1)H NMR, (13)C NMR, and HR-MS techniques. The research focused on assessing these compounds for their toxicity, ability to prevent glycation, antioxidant properties, and their potential to combat hyperlipidemia. Toxicity was evaluated on the 3T3 L1 fibroblast cell line using the MTT assay. The capacity to prevent glycation was tested with bovine serum albumin-methylglyoxal and bovine serum albumin-glucose systems. This study measured total reactive oxygen species in the 3T3 L1 cell line using 2',7'-dichlorodihydrofluorescein diacetate staining, and antioxidant capacity was assessed through DPPH scavenging and metal ion chelation tests. The effectiveness against hyperlipidemia was determined by targeting cholesterol esterase and pancreatic lipase activities, with concentrations of the compounds 5 to 12 ranging from 0.0245 to 0.268 μM. Standard drugs such as orlistat, simvastatin, statins, and aminoguanidine were used as positive controls in various assays. Additionally, computational docking studies with AutoDock Vina were performed. The resulting findings indicated that the compounds were non-toxic to cells, effectively inhibited key enzymes related to hyperlipidemia, and showed significant antioxidant properties, including the prevention of advanced glycation end-product formation. Compounds 11 and 12 demonstrated the highest activity levels. These promising results highlight the potential of new quinobenzothiazine derivatives as lead compounds for the development of antihyperlipidemic drugs, although further research is necessary to confirm their efficacy and safety.