Antiglycation activity of triazole Schiff's bases against fructose-mediated glycation: In vitro and in silico study.

Advanced glycation end products (AGEs) are known to be involved in pathophysiology of diabetic complications, neurodegenerative diseases, and aging. Preventing the formation of AGEs can be helpful in the management of these diseases.Two classes of previously synthesized traizole Schiff's bases (4H-1,2,4-triazole-4-Schiff's bases 1-14, and 4H-1,2,4-triazole-3-Schiff's bases 15-23) were evaluated for their in vitro antiglyaction activity.In vitro fructose-mediated human serum albumin (HSA) glycation assay was employed to assess the antiglycation activity of triazole Schiff's bases. The active compounds were subjected to cytotoxicity analysis by MTT assay on mouse fibroblast (3T3) cell line. Molecular docking and simulation studies were carried out to find out the interactions and stability of compounds with HSA. Antiglycemic and antioxidant potential of active, and non-cytotoxic compounds were evaluated by in vitro α-glucosidase inhibition assay, and DPPH free radical scavenging assay, respectively.Compound 1 (IC50 = 47.30 ± 0.38 µM) from 4H-1,2,4-triazole-4-Schiff's bases exhibited antiglycation activity comparable to standard rutin (IC50 = 54.5 ± 0.05 µM) along with stable RMSD profile in MD simulation studies. Compound 1 also exhibited potent α-glucosidase inhibitory activity and moderate antioxidant property. Other derivatives showed a weak antiglycation activity with IC50 values between 248.1 - 637.7 µM. Compounds with potential antiglycation profile were found to the formation of be non-cytotoxic in cellular assay.The study identifies triazole Schiff's bases active against fructose-mediated glycation of HSA, thus indicates their potential against late diabetic complications due to advanced glycation end products (AGEs).