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Antiglycation Activity of Triazole Schiff's Bases Against Fructosemediated Glycation: In Vitro and In Silico Study
Muniza Shaikh1, Salman Siddiqui2, Humaira Zafar1
1Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
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.
Objectives:
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).
Insights
Triazole Schiff's bases show potential in preventing advanced glycation end products (AGEs) formation, which are linked to diabetic complications. Compound 1 demonstrated significant antiglycation activity and was non-cytotoxic, suggesting therapeutic promise.
Area of Science:
- Medicinal Chemistry
- Biochemistry
- Pharmacology
Background:
- Advanced glycation end products (AGEs) contribute to diabetic complications, neurodegenerative diseases, and aging.
- Inhibiting AGEs formation is a potential therapeutic strategy for managing these conditions.
Purpose of the Study:
- To evaluate the in vitro antiglycation activity of synthesized triazole Schiff's bases.
- To assess the therapeutic potential of these compounds against AGEs-related diseases.
Main Methods:
- In vitro fructose-mediated human serum albumin (HSA) glycation assay.
- Cytotoxicity analysis using MTT assay on 3T3 cell line.
- Molecular docking, simulation, α-glucosidase inhibition, and DPPH radical scavenging assays.
Main Results:
- Compound 1 exhibited significant antiglycation activity (IC50=47.30±0.38 µM), comparable to rutin.
- Compound 1 showed potent α-glucosidase inhibition and moderate antioxidant activity.
- Active compounds were non-cytotoxic, indicating a favorable safety profile.
Conclusions:
- Triazole Schiff's bases are effective inhibitors of fructose-mediated HSA glycation.
- These compounds show promise for managing diabetic complications associated with AGEs production.