An operationally simple one-pot three-component synthesis method for a series of diverse purine analogues of [1,2,4]-triazolo[1,3,5]triazine-2-carboxamide derivatives generated in situ via reaction of 2-hydrazinyl- N -(4-sulfamoylphenyl)-2-thioxoacetamide, cyanoguanidine and a variety of aldehydes.

Background/Objectives: Inflammation is a crucial and complex mechanism that protects the body against infections. In our study, we propose to provide scientific evidence for the anti-inflammatory properties of 1,3,5-triazine derivatives. Methods: Initially, we ensured the safety of the three synthesized derivatives by administering graded doses of up to 2000 mg/kg intraperitoneally in Wistar rats. Thus, the three derivatives were considered generally safe. We also evaluated their ability to reduce carrageenan-induced rat paw edema. Results: Compounds 1, 2, and 3 demonstrated stronger anti-inflammatory activity than indomethacin (10 mg/kg), achieving maximum inhibition at the fourth hour with percentages of 96.31%, 72.08%, and 99.69%, respectively, at a dose of 200 mg/kg, compared to 57.66% for the standard drug. To explore the mechanism, levels of pro-inflammatory cytokines (TNF-α, IL-1α, IL-1β, IL-6, CRP) and oxidative stress markers were measured in paw tissue. All three compounds significantly reduced these markers more effectively than indomethacin and enhanced antioxidant levels (SOD and GSH) beyond those achieved by the standard treatment. Additionally, the compounds reduced COX-1 and COX-2 levels to values comparable to those in the normal (non-inflamed) control group. Conclusions: Compounds 1, 2, and 3 at doses of 200 mg/kg significantly (p < 0.05) inhibited the heat-induced hemolysis of red blood cell (RBC) membranes by 94.6%, 93.9%, and 95.2%, respectively, compared to 94.5% produced by indomethacin. Consequently, we concluded that 1,3,5-triazine derivatives are a safe antioxidant agent with significant anti-inflammatory activity.

Insulin resistance is a primary feature of type 2 diabetes. This study compared the effects of curcumin and its nanoformulation on insulin resistance, fasting blood sugar, liver function, GLUT4, lipid profile, and oxidative stress in the liver and pancreas in a diabetic model. Thirty male Wistar rats were divided into five groups: a control group, a diabetic group, a diabetic group treated with metformin (40 mg/kg), a diabetic group treated with curcumin (100 mg/kg), and a diabetic group treated with curcumin NPs (100 mg/kg). Diabetes was induced by injecting dexamethasone daily for 14 days. Treatment with curcumin and curcumin NPs was administered by gavage for 14 days. Body weight and fasting blood sugar levels were measured on days 1, 14, and 28. The metformin, curcumin, and curcumin NPs groups showed significantly greater body weight gain than the untreated diabetic group (P < 0.001). In diabetic rats treated with curcumin and curcumin NPs, insulin resistance decreased by approximately 40 %, while fasting blood sugar levels dropped by 35–40 % (P < 0.001). The levels of liver enzymes (AST, ALT), cholesterol, triglycerides, LDL, and the oxidative stress marker MDA in liver and pancreatic tissues were reduced by 30–50 %. Additionally, beneficial markers such as albumin, HDL, antioxidants (GSH, SOD), and GLUT4 levels were increased by 25–45 % (P < 0.001). Nano-curcumin consistently showed greater improvements than curcumin, especially in reducing oxidative stress and supporting liver and pancreatic health. This study demonstrates that curcumin NPs has a superior effect on reducing oxidative stress and improving metabolic parameters in diabetes compared to curcumin. by enhancing the bioavailability and stability of curcumin, the nanoformulation showed stronger therapeutic potential for managing high blood sugar, cholesterol issues, and liver health, positioning curcumin NPs as a promising alternative to conventional treatments for diabetes and its complications.