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

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. 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).

Synthesis of Fluorinated Hydrazinylthiazole Derivatives: A Virtual and Experimental Approach to Diabetes Management

“…This binding site includes a part of Sudlow site I, where Lys 199 is responsible for 5% of the total glycation. , In vitro results also corroborate the best IC 50 obtained with the same ligands exhibiting the highest binding energy in the in silico studies. Previously, triazole-based Schiff bases and thiazole-based thiosemicarbazones had shown antiglycation activities by in silico studies …”

“…Previously, triazole-based Schiff bases and thiazole-based thiosemicarbazones had shown antiglycation activities by in silico studies. 46 …”

“…Previously, triazole-based Schiff bases and thiazole-based thiosemicarbazones had shown antiglycation activities by in silico studies. 46 Human pancreatic α-amylase (HPA) has multiple ligand binding sites in its three-domain structure. 47,48 Ligands 3a−o have been found to interact in four of these sites, with the binding energies ranging from −8.78 to −7.22 kcal/mol (Table 6).…”

Anti-Tubercular Properties of 4-Amino-5-(4-Fluoro-3- Phenoxyphenyl)-4H-1,2,4-Triazole-3-Thiol and Its Schiff Bases: Computational Input and Molecular Dynamics

“…Based on the last 40 years of academic and pharmaceutical industry inventions, only bedaquiline was the first novel anti-TB drug permitted by the United States Food and Drug Administration (US FDA) authority in December 2012, for the treatment of MDR-TB, [6] while delamanid was the second anti-TB agent to be approved by the European Medicines Agency in late 2013 [7] and pretomanid was the third drug to be approved by the US FDA in August 2019 [8,9] (Figure 1). Triazole pharmacophore with various functional groups/substitutions has been reported for its promising anti-TB [10][11][12][13][14][15][16][17][18][19][20][21], antiviral [22], antibacterial [23,24], antifungal [25,26], antioxidant [27][28][29][30], and antiglycation properties [31]. In addition, it also serves as an opener of Ca( 2+ )-activated potassium (maxi-K) channels [32] and demonstrates molluscicidal [33], hypoglycemic [34], antihypertensive and blood platelet aggregation inhibition [35] activities.…”

“…Triazole pharmacophore with various functional groups/substitutions has been reported for its promising anti-TB [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], antiviral [ 22 ], antibacterial [ 23 , 24 ], antifungal [ 25 , 26 ], antioxidant [ 27 , 28 , 29 , 30 ], and antiglycation properties [ 31 ]. In addition, it also serves as an opener of Ca( 2+ )-activated potassium (maxi-K) channels [ 32 ] and demonstrates molluscicidal [ 33 ], hypoglycemic [ 34 ], antihypertensive and blood platelet aggregation inhibition [ 35 ] activities.…”