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<p>This study explores the potential of selected natural products from <i>Harungana madagascariensis</i> (namely: harunganin anthrone, madagascin anthrone, harongin anthrone, harunmadagascarins-A, harunmadagascarins-B, kenganthranol-A, kenganthranol-B, kenganthranol-C, harunganol-A, harunganol-B, harunganol-D, harunganol E, harunganol-C, kengaquinone, madagascin, physcion, chrysophanol, madagascol, vismiaquinone-A, vismiaquinone-B, vismiaquinone-C, euxanthone, cadensin C, friedelan-3-one, lupeol, betulinic acid, kaempferol-3-O-β-D-glucopyranoside and methyl-<i>3</i>-formyl-<i>2</i>,<i>4</i>-dihydroxy-<i>6</i>-methyl benzoate) as inhibitors of bio-film formation response regulator (BfmR), a key virulence-associated response regulator in <i>Acinetobacter baumannii</i> (one of the ESKAPE pathogens).We employed integrative computational approach encompassing molecular docking, drug-likeness screening, ADMET profiling, molecular dynamics (MD) simulations, and Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) free energy calculations for this assessment. Molecular docking indicated strong binding affinities at the BfmR homodimer interface, with the obtained docking scores surpassing that of the reference antibiotic, ofloxacin. Five top-performing compounds—harunganol-B, madagascin, madagascol, vismiaquinone-B and vismiaquinone-C were identified as potential inhibitors which showed properties compliant with Lipinski’s Rule of Five. They also showed favorable gastrointestinal absorption and blood-brain barrier permeability profiles, as revealed by the BOILED-Egg model. MD simulations confirmed the structural stability of ligand-protein complexes, showing minimal RMSD and enhanced compactness and residue rigidity upon ligand binding. MM/PBSA analyses further supported the stability of the complexes, with harunganol-B demonstrating the most favorable binding free energy (ΔG_bind = − 50.12&#xa0;kcal/mol). Overall, the computational data obtained underscore the promising inhibitory potential of these compounds, particularly harunganol-B, and highlighted their suitability for future in vitro and in vivo validation as lead scaffolds in anti-<i>A. baumannii</i> drug development.</p>

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Harunganol-B and beyond: unveiling nature’s arsenal against drug-resistant Acinetobacter baumannii

  • 期刊论文

  • 发表日期：

    2026年2月4日

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  • Kola A. Oluwafemi,
  • Wande M. Oluyemi,
  • Adebisi Olonisakin,
  • Jane A. Aigbogun,
  • Shadrach C. Eze,
  • Adeniyi T. Adewumi,
  • Salerwe Mosebi,
  • Oluwakayode O. Odeja,
  • Rashidat B. Jimoh,
  • Emmanuel O. Akele

摘要

This study explores the potential of selected natural products from Harungana madagascariensis (namely: harunganin anthrone, madagascin anthrone, harongin anthrone, harunmadagascarins-A, harunmadagascarins-B, kenganthranol-A, kenganthranol-B, kenganthranol-C, harunganol-A, harunganol-B, harunganol-D, harunganol E, harunganol-C, kengaquinone, madagascin, physcion, chrysophanol, madagascol, vismiaquinone-A, vismiaquinone-B, vismiaquinone-C, euxanthone, cadensin C, friedelan-3-one, lupeol, betulinic acid, kaempferol-3-O-β-D-glucopyranoside and methyl-3-formyl-2,4-dihydroxy-6-methyl benzoate) as inhibitors of bio-film formation response regulator (BfmR), a key virulence-associated response regulator in Acinetobacter baumannii (one of the ESKAPE pathogens).We employed integrative computational approach encompassing molecular docking, drug-likeness screening, ADMET profiling, molecular dynamics (MD) simulations, and Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) free energy calculations for this assessment. Molecular docking indicated strong binding affinities at the BfmR homodimer interface, with the obtained docking scores surpassing that of the reference antibiotic, ofloxacin. Five top-performing compounds—harunganol-B, madagascin, madagascol, vismiaquinone-B and vismiaquinone-C were identified as potential inhibitors which showed properties compliant with Lipinski’s Rule of Five. They also showed favorable gastrointestinal absorption and blood-brain barrier permeability profiles, as revealed by the BOILED-Egg model. MD simulations confirmed the structural stability of ligand-protein complexes, showing minimal RMSD and enhanced compactness and residue rigidity upon ligand binding. MM/PBSA analyses further supported the stability of the complexes, with harunganol-B demonstrating the most favorable binding free energy (ΔG_bind = − 50.12 kcal/mol). Overall, the computational data obtained underscore the promising inhibitory potential of these compounds, particularly harunganol-B, and highlighted their suitability for future in vitro and in vivo validation as lead scaffolds in anti-A. baumannii drug development.