Background:
Advanced glycation end products (AGEs) are known to be involved in the
pathophysiology of diabetic complications, neurodegenerative diseases, and aging. Preventing the
formation of AGEs can be helpful in the management of these diseases.
Objective:
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
antiglycation activity.
Methods:
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 evaluate the interactions and stability of compounds with
HSA. Anti-hyperglycemic and antioxidant activities of selected non-cytotoxic compounds were
evaluated by in vitro α-glucosidase inhibition, and DPPH free radical scavenging assays,
respectively.
Results:
Compound 1 (IC50=47.30±0.38 µM) from 4H-1,2,4-triazole-4-Schiff’s bases has
exhibited antiglycation activity comparable to standard rutin (IC50=54.5±0.05 µM) along with a
stable RMSD profile in MD simulation studies. Compound 1 also exhibited a 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 be non-cytotoxic in a cellular assay.
Conclusion:
The study identifies triazole Schiff’s bases active against fructose-mediated glycation
of HSA, thus indicates their potential against late diabetic complications due to production of advancedend
products (AGEs).