Synthesis, Biological Evaluation, and Molecular Docking Studies of New Nitro Vanillin Analogues as Anti-glycating Agents

Abstract

Persistent hyperglycemia is linked to a range of chronic complications in diabetes, such as neuropathy, retinopathy, nephropathy, and atherosclerosis. The underlying cause is the highly stable advanced glycation end products (AGEs) resulting from prolonged exposure to high glucose level. Hence the present study was undertaken on the anti-glycation activity of a series of synthetic analogues (Schiff bases) 4a-4o of nitrovanillin synthesized by its coupling with different amino reagents. Nitrovanillin was obtained by the nitration of vanillin. Vanillin is a natural product that was obtained by the reduction of vanillic acid. Vanillic acid is another natural product which was isolated from ethanol extract of plant species Tamarix aphylla during the current study. These analogues were screened for in-vitro anti-glycation activity using rutin (IC50 = 180±0.8 µM) as a reference molecule. The best potent analogues 4a (IC50 = 121±1.0 µM), 4f (IC50 = 95.0±0.7 µM), and 4h (IC50 = 183±3.8 µM) were subjected to computational study that revealed they were not only anti-glycation active, but also having well in ligand–protein interaction profile. While, all others analogues were found moderate to highly active. When the safety profile of these analogues 4a-4o was evaluated by MTT assay using HepG2 cells against doxorubicin as a reference drug, the analogues 4a, 4e, 4f, 4i, 4l, 4m, and 4o were found nontoxic, while analogues 4d, 4h, 4k, and 4n showed insignificant toxicity.

Keywords

• AGEs
• Amadori product
• Anti-glycation
• Column chromatography
• Docking study
• Tamarix aphylla

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