Structure-Based Virtual Screening of Enantia chlorantha Stem Bark Constituents Reveals Candidate Pancreatic Alpha-Amylase Inhibitors
5 affiliations
- 1Federal College of Veterinary and Medical Laboratory Technology Vom
- 2Federal University of Medical Sciences
- 3West African Centre for Cell Biology of Infectious Pathogens (WACCBIP
- 4University of Ghana
- 5National Veterinary Research Institute (NVRI
Abstract
Type 2 diabetes mellitus (T2DM) remains a major global health burden, and inhibition of pancreatic alpha-amylase is an established strategy for limiting postprandial hyperglycaemia. Enantia chlorantha stem bark is widely used in Nigerian ethnomedicine, but its alpha-amylase-inhibitory phytoconstituents have not been characterised at the molecular level. This study applied structure-based computational screening to identify candidate alpha-amylase inhibitors from E. chlorantha stem bark, using a previously reported GC-MS phytochemical profile of a carbonated stem-bark extract as the source of the screened ligand library. The GC-MS-identified constituents were docked against human pancreatic alpha-amylase (PDB ID: 1B2Y) using Glide, followed by induced fit docking (IFD) of the top-ranked hits and ADMET prediction (SwissADME, ProTox-III). Neoisolongifolene-8-ol emerged as the most promising hit, with a docking score of −6.201 kcal/mol. To assess the physical plausibility of this predicted interaction, a 10 ns all-atom molecular dynamics (MD) simulation of the enzyme–Neoisolongifolene-8-ol complex was performed in GROMACS 2024.5 with the CHARMM36m force field. The complex remained conformationally stable throughout the simulation (mean backbone RMSD = 1.17 ± 0.13 Å; mean radius of gyration = 2.352 ± 0.008 nm), with a well-maintained intramolecular hydrogen-bonding network (384.8 ± 8.7 bonds) and narrow solvent-accessible surface area fluctuation (201.5 ± 2.4 nm2). The ligand hydroxyl group formed a persistent hydrogen bond with the active-site residue His305, and principal component analysis indicated smooth, non-oscillatory conformational sampling consistent with a stable binding mode. These findings provide converging docking- and dynamics-level evidence that Neoisolongifolene-8-ol is a computationally predicted, structurally stable ligand of pancreatic alpha-amylase. As a purely in silico prediction, this finding does not establish therapeutic efficacy; in vitro kinetic and in vivo validation of this and related E. chlorantha stem bark constituents remain necessary before any candidate can be considered for T2DM management.
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BibTeX
@misc{mark2026structurebased,
title = {{Structure-Based Virtual Screening of Enantia chlorantha Stem Bark Constituents Reveals Candidate Pancreatic Alpha-Amylase Inhibitors}},
author = {Olumuyiwa Mark ADU and Gabriel Akinwale SOTADE and Titilayo JOHNSON and Gbolahan ODUSELU and Matthew Egbono OTOR},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010539/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010539/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Structure-Based Virtual Screening of Enantia chlorantha Stem Bark Constituents Reveals Candidate Pancreatic Alpha-Amylase Inhibitors
AU - Olumuyiwa Mark ADU
AU - Gabriel Akinwale SOTADE
AU - Titilayo JOHNSON
AU - Gbolahan ODUSELU
AU - Matthew Egbono OTOR
PY - 2026
DA - 2026/10/15
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010539/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010539/v1
AB - Type 2 diabetes mellitus (T2DM) remains a major global health burden, and inhibition of pancreatic alpha-amylase is an established strategy for limiting postprandial hyperglycaemia. Enantia chlorantha stem bark is widely used in Nigerian ethnomedicine, but its alpha-amylase-inhibitory phytoconstituents have not been characterised at the molecular level. This study applied structure-based computational screening to identify candidate alpha-amylase inhibitors from E. chlorantha stem bark, using a previously reported GC-MS phytochemical profile of a carbonated stem-bark extract as the source of the screened ligand library. The GC-MS-identified constituents were docked against human pancreatic alpha-amylase (PDB ID: 1B2Y) using Glide, followed by induced fit docking (IFD) of the top-ranked hits and ADMET prediction (SwissADME, ProTox-III). Neoisolongifolene-8-ol emerged as the most promising hit, with a docking score of −6.201 kcal/mol. To assess the physical plausibility of this predicted interaction, a 10 ns all-atom molecular dynamics (MD) simulation of the enzyme–Neoisolongifolene-8-ol complex was performed in GROMACS 2024.5 with the CHARMM36m force field. The complex remained conformationally stable throughout the simulation (mean backbone RMSD = 1.17 ± 0.13 Å; mean radius of gyration = 2.352 ± 0.008 nm), with a well-maintained intramolecular hydrogen-bonding network (384.8 ± 8.7 bonds) and narrow solvent-accessible surface area fluctuation (201.5 ± 2.4 nm2). The ligand hydroxyl group formed a persistent hydrogen bond with the active-site residue His305, and principal component analysis indicated smooth, non-oscillatory conformational sampling consistent with a stable binding mode. These findings provide converging docking- and dynamics-level evidence that Neoisolongifolene-8-ol is a computationally predicted, structurally stable ligand of pancreatic alpha-amylase. As a purely in silico prediction, this finding does not establish therapeutic efficacy; in vitro kinetic and in vivo validation of this and related E. chlorantha stem bark constituents remain necessary before any candidate can be considered for T2DM management.
ER -