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In Silico and In Vitro Analyses to Repurpose Quercetin as a Human Pancreatic α-Amylase Inhibitor
[Image: see text] Human pancreatic α-amylase (HPA), situated at the apex of the starch digestion hierarchy, is an attractive therapeutic approach to precisely regulate blood glucose levels, thereby efficiently managing diabetes. Polyphenols offer a natural and multifaceted approach to moderate postp...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666247/ https://www.ncbi.nlm.nih.gov/pubmed/38027372 http://dx.doi.org/10.1021/acsomega.3c05082 |
Sumario: | [Image: see text] Human pancreatic α-amylase (HPA), situated at the apex of the starch digestion hierarchy, is an attractive therapeutic approach to precisely regulate blood glucose levels, thereby efficiently managing diabetes. Polyphenols offer a natural and multifaceted approach to moderate postprandial sugar spikes, with their slight modulation in carbohydrate digestion and potential secondary benefits, such as antioxidant and anti-inflammatory effects. Taking into consideration the unfavorable side effects of currently available commercial medications, we aimed to study a library of polyphenols attributed to their remarkable antidiabetic properties and screened the most potent HPA inhibitor via a comprehensive in silico study encompassing molecular docking, molecular mechanics with generalized Born and surface area solvation (MM/GBSA) calculation, molecular dynamics (MD) simulation, density functional theory (DFT) study, and pharmacokinetic properties followed by an in vitro assay. Significant hydrogen bonding with the catalytic triad residues of HPA, prominent MM/GBSA binding energy of −27.03 kcal/mol, and the stable nature of the protein–ligand complex with regard to 100 ns MD simulation screened quercetin as the best HPA inhibitor. Additionally, quercetin showed strong reactivity in the substrate-binding pocket of HPA and exhibited favorable pharmacokinetic properties with a considerable inhibitory concentration (IC(50)) of 57.37 ± 0.9 μg/mL against α-amylase. This study holds prospects for HPA inhibition and suggests quercetin as an approach to therapy for diabetes; however, it is imperative to conduct further research. |
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