Unrevealed oligoresveratrols from Shorea parvifolia root bark as xanthine oxidase inhibitors: isolation, in vitro bioassay, quantum studies and structure-based computational profiling
6 affiliations
- 1Doctoral Program of Mathematics and Natural Sciences, Faculty of Science and Technology, Universitas Airlangga Surabaya 60115 Indonesia.
- 2Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga Surabaya 60115 Indonesia [email protected].
- 3Biotechnology of Tropical Medicinal Plants Research Group, Universitas Airlangga Surabaya 60115 Indonesia.
- 4Bioinformatic Laboratory, UCoE Research Center for Bio-Molecule Engineering, Universitas Airlangga Surabaya 60115 Indonesia.
- 5Faculty of Pharmacy, Meijo University 150 Yagotoyama, Tempaku Nagoya 468-8503 Japan.
- 6Department of Chemistry, Faculty of Mathematics & Natural Sciences, Universitas Negeri Surabaya Surabaya 60231 Indonesia.
Abstract
Resveratrol oligomers from Shorea species possess diverse biological activities, but the structural determinants governing their inhibition of xanthine oxidase (XO) remain poorly understood. This study investigated oligoresveratrols isolated from the root bark of Shorea parvifolia and examined how their structures relate to XO inhibitory potential. Five oligoresveratrols were isolated and structurally characterized by spectroscopic analysis. We evaluated their XO inhibitory activities, followed by pharmacokinetic and drug-likeness predictions, DFT calculations, molecular docking, and molecular dynamics simulations of the most active compounds. Five compounds, including isoampelopsin D (1), diptoindonesin G (2), shorealactone (3), α-viniferin (4), and neohopeaphenol A (5), were identified. XO inhibition varied substantially among the compounds, with shorealactone (3) showing the strongest activity (IC₅₀ = 32.53 µM), outperforming the clinical reference standard, allopurinol (40.1 µM). Isoampelopsin D (1) also showed potent inhibition (65.15 µM), whereas diptoindonesin G (2) showed the weakest activity in the series (161.08 µM). Docking identified favorable interactions of compounds 1-3 within the molybdopterin domain of XO, while molecular dynamics provided compound stability during 100 ns simulations. MM-PBSA calculations yielded favorable binding free energies for compounds 2, 1, and 3, with ΔG bind values of -18.03, -17.17, and -14.36 kcal mol⁻¹, respectively, compared with -9.9972 kcal mol⁻¹ for allopurinol. However, compound 3 achieves the most favorable thermodynamic affinity (ΔG exp = -6.12 kcal mol⁻¹), outperforming allopurinol (-6.00 kcal mol⁻¹). This is followed by compound 1 (-5.71 kcal mol⁻¹) and compound 2 (-5.17 kcal mol⁻¹). Collectively, these divergent bioactivity profiles identify isoampelopsin D (1) and shorealactone (3) as promising structural scaffolds for future development as natural xanthine oxidase inhibitors.
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BibTeX
@article{windah2026unrevealed,
title = {{Unrevealed oligoresveratrols from Shorea parvifolia root bark as xanthine oxidase inhibitors: isolation, in vitro bioassay, quantum studies and structure-based computational profiling}},
author = {Axl Laurens Lukas Windah and Nanik Siti Aminah and Alfinda Novi Kristanti and Imam Siswanto and Geraldo Figo Hariyanto and Titah Aldila Budiastanti and Yoshiaki Takaya and Muhammad Ikhlas Abdjan},
journal = {RSC advances},
year = {2026},
month = nov,
doi = {10.1039/d6ra07686f},
url = {https://europepmc.org/article/PMC/PMC13725863},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Unrevealed oligoresveratrols from Shorea parvifolia root bark as xanthine oxidase inhibitors: isolation, in vitro bioassay, quantum studies and structure-based computational profiling
AU - Axl Laurens Lukas Windah
AU - Nanik Siti Aminah
AU - Alfinda Novi Kristanti
AU - Imam Siswanto
AU - Geraldo Figo Hariyanto
AU - Titah Aldila Budiastanti
AU - Yoshiaki Takaya
AU - Muhammad Ikhlas Abdjan
PY - 2026
DA - 2026/11/02
JO - RSC advances
DO - 10.1039/d6ra07686f
UR - https://europepmc.org/article/PMC/PMC13725863
AB - Resveratrol oligomers from Shorea species possess diverse biological activities, but the structural determinants governing their inhibition of xanthine oxidase (XO) remain poorly understood. This study investigated oligoresveratrols isolated from the root bark of Shorea parvifolia and examined how their structures relate to XO inhibitory potential. Five oligoresveratrols were isolated and structurally characterized by spectroscopic analysis. We evaluated their XO inhibitory activities, followed by pharmacokinetic and drug-likeness predictions, DFT calculations, molecular docking, and molecular dynamics simulations of the most active compounds. Five compounds, including isoampelopsin D (1), diptoindonesin G (2), shorealactone (3), α-viniferin (4), and neohopeaphenol A (5), were identified. XO inhibition varied substantially among the compounds, with shorealactone (3) showing the strongest activity (IC₅₀ = 32.53 µM), outperforming the clinical reference standard, allopurinol (40.1 µM). Isoampelopsin D (1) also showed potent inhibition (65.15 µM), whereas diptoindonesin G (2) showed the weakest activity in the series (161.08 µM). Docking identified favorable interactions of compounds 1-3 within the molybdopterin domain of XO, while molecular dynamics provided compound stability during 100 ns simulations. MM-PBSA calculations yielded favorable binding free energies for compounds 2, 1, and 3, with ΔG bind values of -18.03, -17.17, and -14.36 kcal mol⁻¹, respectively, compared with -9.9972 kcal mol⁻¹ for allopurinol. However, compound 3 achieves the most favorable thermodynamic affinity (ΔG exp = -6.12 kcal mol⁻¹), outperforming allopurinol (-6.00 kcal mol⁻¹). This is followed by compound 1 (-5.71 kcal mol⁻¹) and compound 2 (-5.17 kcal mol⁻¹). Collectively, these divergent bioactivity profiles identify isoampelopsin D (1) and shorealactone (3) as promising structural scaffolds for future development as natural xanthine oxidase inhibitors.
SN - 2046-2069
ER -