Antiglycation Activity of Triazole Schiff’s Bases Against Fructosemediated Glycation: In Vitro and In Silico Study

Author(s): Muniza Shaikh, Salman Siddiqui, Humaira Zafar, Uzma Naqeeb, Fakiha Subzwari, Rehan Imad, Khalid M. Khan, Muhammad I. Choudhary*

Journal Name: Medicinal Chemistry

Volume 16 , Issue 4 , 2020

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Graphical Abstract:


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).

Keywords: Antiglycation activity, triazole Schiff's bases, diabetes, fructose, rutin, human serum albumin.

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Year: 2020
Published on: 21 May, 2020
Page: [575 - 591]
Pages: 17
DOI: 10.2174/1573406415666190212105718
Price: $65

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