Discovery of novel glucosinolates inhibiting advanced glycation end products: Virtual screening and molecular dynamic simulation

Abstract Protein glycation can result in the formation of advanced glycation end products (AGEs), which pose a potential health risk due to their association with diabetic complications. Natural products are a source of drugs discovery and the search for potential natural inhibitors of AGEs is of great significance. Glucosinolates (GSLs) mainly from cruciferous plants have potential antioxidant, anti‐inflammatory, and anti‐glycation activities. In this study, the inhibitory activity of GSLs on bovine serum albumin (BSA) along with its mechanism was investigated by virtual screening and various computational simulation techniques. Virtual screening revealed that 174 GSLs were screened using Maestro based on the glide score and 89% of the compounds were found to have potential anti‐glycation ability with the docking scores less than −5 kcal/mol. Molecular docking showed that the top 10 GSLs were bound to the IIA structural domain of BSA. Among them, glucohesperin ( 1 ) and 2‐hydroxyethyl glucosinolate ( 2 ) had the lowest docking scores of −9.428 and −9.333 kcal/mol, respectively, reflecting their good binding affinity. Molecular dynamics simulations of 1 (Δ G = −43.46 kcal/mol) and 2 (Δ G = −43.71 kcal/mol) revealed that the complexes of these two compounds with proteins had good stability. Further binding site analysis suggested that the mechanism of inhibition of protein glycation by these two active ingredients might be through competitive hydrogen bonding to maintain the structural integrity of the protein, thus inhibiting glycation reaction. Moreover, the ADMET values and CYP450 metabolism prediction data were within the recommended values. Therefore, it can be concluded that 1 and 2 may act as potential anti‐glycation agents.