Electronic structure, topological analysis, molecular docking and ADMET of a bioactive flavonoid glycoside from Dicranopteris linearis
- 1Department of Chemistry, Ho Chi Minh City University of Education 280 An Duong Vuong Street, Cho Quan Ward Ho Chi Minh City 748342 Vietnam
Abstract
Kaempferol-3-O-(4″,6″-di-E-p-coumaroyl)-β-d-glucopyranoside (1), recently isolated from Dicranopteris linearis, exhibits α-glucosidase inhibitory activity, but the molecular features underlying this activity remain unclear. Here, density functional theory (DFT) was integrated with frontier molecular orbital (FMO), molecular electrostatic potential (MEP), quantum theory of atoms in molecules (QTAIM), non-covalent interaction (NCI), natural population (NPA), CLPO charge-transfer, electron localization function (ELF), localized orbital locator (LOL) and harmonic oscillator model of aromaticity (HOMA) analyses to characterize the electronic and topological architecture of 1. The HOMO and LUMO are predominantly associated with the two p-coumaroyl substituents, whereas the chromone C2
Created by potrace 1.16, written by Peter Selinger 2001-2019
C3–C4O unit contributes 61.1% to the LUMO+1. ELF and LOL analyses complemented this picture by characterizing electron localization across the molecule. QTAIM/NCI further identified a differentiated network of weak closed-shell interactions, whereas MEP highlighted carbonyl- and hydroxyl-centered electrostatic hot spots. NPA and CLPO charge-transfer analysis showed a push–pull chromone, a resonance-assisted 5-OH⋯OC4 hydrogen bond and no through-space charge transfer between the π-stacked coumaroyl groups. Molecular docking against processing α-glucosidase I from Saccharomyces cerevisiae (PDB ID: 4J5T), providing the primary structural context for the experimentally reported α-glucosidase inhibitory activity (IC50 = 22.5 µM) and exploratory docking against human maltase–glucoamylase (MGAM; PDB ID: 3TOP), suggested preliminary binding poses involving key pocket residues and complementary hydrogen-bonding, π-mediated, and hydrophobic contacts. The electronic features identified computationally provide an electronic framework for interpreting the experimentally reported α-glucosidase inhibitory activity. ADMET profiling additionally indicated limited passive permeability and negligible predicted CNS exposure.
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BibTeX
@article{do2026electronic,
title = {{Electronic structure, topological analysis, molecular docking and ADMET of a bioactive flavonoid glycoside from Dicranopteris linearis}},
author = {Ky A. Do},
journal = {RSC Advances},
year = {2026},
month = nov,
doi = {10.1039/d6ra08672a},
url = {https://doi.org/10.1039/d6ra08672a},
note = {CC BY-NC 3.0},
}
RIS
TY - JOUR
TI - Electronic structure, topological analysis, molecular docking and ADMET of a bioactive flavonoid glycoside from Dicranopteris linearis
AU - Ky A. Do
PY - 2026
DA - 2026/11/05
JO - RSC Advances
DO - 10.1039/d6ra08672a
UR - https://doi.org/10.1039/d6ra08672a
AB - Kaempferol-3-O-(4″,6″-di-E-p-coumaroyl)-β-d-glucopyranoside (1), recently isolated from Dicranopteris linearis, exhibits α-glucosidase inhibitory activity, but the molecular features underlying this activity remain unclear. Here, density functional theory (DFT) was integrated with frontier molecular orbital (FMO), molecular electrostatic potential (MEP), quantum theory of atoms in molecules (QTAIM), non-covalent interaction (NCI), natural population (NPA), CLPO charge-transfer, electron localization function (ELF), localized orbital locator (LOL) and harmonic oscillator model of aromaticity (HOMA) analyses to characterize the electronic and topological architecture of 1. The HOMO and LUMO are predominantly associated with the two p-coumaroyl substituents, whereas the chromone C2 Created by potrace 1.16, written by Peter Selinger 2001-2019 C3–C4O unit contributes 61.1% to the LUMO+1. ELF and LOL analyses complemented this picture by characterizing electron localization across the molecule. QTAIM/NCI further identified a differentiated network of weak closed-shell interactions, whereas MEP highlighted carbonyl- and hydroxyl-centered electrostatic hot spots. NPA and CLPO charge-transfer analysis showed a push–pull chromone, a resonance-assisted 5-OH⋯OC4 hydrogen bond and no through-space charge transfer between the π-stacked coumaroyl groups. Molecular docking against processing α-glucosidase I from Saccharomyces cerevisiae (PDB ID: 4J5T), providing the primary structural context for the experimentally reported α-glucosidase inhibitory activity (IC50 = 22.5 µM) and exploratory docking against human maltase–glucoamylase (MGAM; PDB ID: 3TOP), suggested preliminary binding poses involving key pocket residues and complementary hydrogen-bonding, π-mediated, and hydrophobic contacts. The electronic features identified computationally provide an electronic framework for interpreting the experimentally reported α-glucosidase inhibitory activity. ADMET profiling additionally indicated limited passive permeability and negligible predicted CNS exposure.
SN - 2046-2069
ER -