Structure‐Based Virtual Screening, ADMET analysis, and Molecular Dynamics Simulation of Moroccan Natural Compounds as Candidates α‐Amylase Inhibitors

Abstract

Current treatments for diabetes mellitus are ineffective, as evidenced by the rise in diabetes cases. This has forced researchers to develop novel chemicals as drugs to block the enzyme alpha-amylase as the severe way to treat diabetes disease. Many previous studies were done to determine the biological activity of a set of molecules isolated from medicinal plants. Morocco is renowned for the abundance of plants it has and for the traditional medical uses of these plants, which drives us to employ our cultural heritage and the variety of our nation's natural resources in the therapeutic area. In the current study, extensive research was conducted to compile a group of phytoconstituents derived from Moroccan plants and used in conventional Moroccan medicine to treat local illnesses. To assess the stability of the generated complexes, molecular docking of the investigated compounds was carried out in the active site of 4 distinct alpha-amylase proteins. The remaining compounds with a high negative binding affinity were then subjected to the ADMET analysis to determine their pharmacological characteristics. The findings showed that two drugs have strong binding affinity for the target proteins and may be used orally as potential alpha-amylase inhibitors. The results of molecular dynamics analysis and MMGBSA calculation were used to validate the optimal stability of created complexes (L97 with studied proteins 1HNY, 1OSE, 1UA7 and 1BAG).

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“…We performed MD simulation to gain insights into the dynamic behaviors of atoms within protein targets and their complexes with ligands, as previously demonstrated. 65 , 79 , 80 This method provides valuable information regarding the structural stability of both the target proteins and ligands, both before and after their interaction, as highlighted by De Vivo et al. 81 Notably, the RMSD of SmGST backbone atoms for both the apo form and the SmGST-17a complex was assessed to understand the dynamics of ligand binding ( Figure 8 A).…”

The Synergistic Influence of Polyflavonoids from Citrus aurantifolia on Diabetes Treatment and Their Modulation of the PI3K/AKT/FOXO1 Signaling Pathways: Molecular Docking Analyses and In Vivo Investigations

“…Previous studies on medicinal plants have described ligand pocket areas as the leading framework for figuring out the target protein active sites of drugs derived from plants efficiently [ 28 ]. Mainly, the docking protocol proceeds via a crucial path for highly effective results [ 29 ].…”