Current computer-aided drug design · 2026
In silico and Network Pharmacology Identification of Acacia senegal Phytochemicals as Potential α-Amylase Inhibitors.
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Abdu Abdulkadir, Bakrey Hossamaldeen, Rikabi Hind A, Ali Amani Ahmed Osman, Abdelrahim Israa, Abdulkareem Eman M, Eltaib Lina
Аннотация
INTRODUCTION: Diabetes mellitus is a rapidly expanding chronic disease, prompting interest in plant-derived natural products as adjuncts to conventional therapy because of their improvements in glycaemic control and reduced complications. To evaluate phytochemicals' potential as α-amylase inhibitors using an integrated in-silico workflow.
METHODS: Acacia senegal phytochemicals retrieved from the IMPPAT 2.0 database were evaluated their in-silico studies against α-amylase inhibitors using molecular docking, DFT, pharmacokinetic and toxicity profiling, in addition to PASS prediction, network pharmacology and MD simulations.
RESULTS: Docking of 31 compounds was carried out, and the top three ligands, which are: IMPHY014840 (-9.321 kcal/mol), IMPHY014838 (-9.208 kcal/mol) and IMPHY006972 (-9.026 kcal/mol), were selected. Their favorable binding energies indicated strong predicted affinity toward the selected enzyme target. DFT calculations showed identical HOMO-LUMO gaps of 6.936 eV for the first two ligands, whereas the third one displayed a larger gap of 9.484 eV, indicating lower chemical reactivity. Furthermore, pharmacokinetic screening indicated high human intestinal absorption (75-86 %) and favorable Caco-2 permeability for the top three compounds, particularly for IMPHY014840 and IMPHY014838. PASS analysis suggested protease target affinity for IMPHY014840 and GPCR/transcription factor activity for IMPHY014838, expanding their therapeutic scope beyond α-amylase inhibition. MD trajectories confirmed overall complex stability, with IMPHY014838 exhibiting marginally lower ligand RMSD and therefore slightly superior dynamical stability.
DISCUSSION: The present study identified IMPHY014840 and IMPHY014838 as promising α- amylase inhibitors, with docking scores of -9.321 and -9.208 kcal/mol, respectively. DFT, ADMET, toxicity, PASS, and 100 ns MD simulations indicate stable enzyme-ligand binding, high predicted intestinal absorption, and multitarget potential. Network pharmacology further suggests that these compounds act on a broad set of diabetes related targets, supporting their value as antidiabetic lead candidates.
CONCLUSION: The combined computational evidence supports IMPHY014840 and IMPHY014838 as promising natural α-amylase inhibitors for type 2 DM management, and recommends in vitro, in vivo, and formulation optimization to address their limitations.
METHODS: Acacia senegal phytochemicals retrieved from the IMPPAT 2.0 database were evaluated their in-silico studies against α-amylase inhibitors using molecular docking, DFT, pharmacokinetic and toxicity profiling, in addition to PASS prediction, network pharmacology and MD simulations.
RESULTS: Docking of 31 compounds was carried out, and the top three ligands, which are: IMPHY014840 (-9.321 kcal/mol), IMPHY014838 (-9.208 kcal/mol) and IMPHY006972 (-9.026 kcal/mol), were selected. Their favorable binding energies indicated strong predicted affinity toward the selected enzyme target. DFT calculations showed identical HOMO-LUMO gaps of 6.936 eV for the first two ligands, whereas the third one displayed a larger gap of 9.484 eV, indicating lower chemical reactivity. Furthermore, pharmacokinetic screening indicated high human intestinal absorption (75-86 %) and favorable Caco-2 permeability for the top three compounds, particularly for IMPHY014840 and IMPHY014838. PASS analysis suggested protease target affinity for IMPHY014840 and GPCR/transcription factor activity for IMPHY014838, expanding their therapeutic scope beyond α-amylase inhibition. MD trajectories confirmed overall complex stability, with IMPHY014838 exhibiting marginally lower ligand RMSD and therefore slightly superior dynamical stability.
DISCUSSION: The present study identified IMPHY014840 and IMPHY014838 as promising α- amylase inhibitors, with docking scores of -9.321 and -9.208 kcal/mol, respectively. DFT, ADMET, toxicity, PASS, and 100 ns MD simulations indicate stable enzyme-ligand binding, high predicted intestinal absorption, and multitarget potential. Network pharmacology further suggests that these compounds act on a broad set of diabetes related targets, supporting their value as antidiabetic lead candidates.
CONCLUSION: The combined computational evidence supports IMPHY014840 and IMPHY014838 as promising natural α-amylase inhibitors for type 2 DM management, and recommends in vitro, in vivo, and formulation optimization to address their limitations.