In silico evaluation of novel metabolites from Tricholoma pardinum: Insights into drug-likeness, toxicity and target interactions via molecular docking and dynamics.
Aug 2026· Technology and Health Care· pp.
9287329261472774
· 0 citations· 31 references
Medicine
TL;DR
Six previously uncharacterized metabolites isolated from the poisonous mushroom Tricholoma pardinum are investigated using an integrated in silico approach to evaluate their therapeutic potential, highlighting the potential of metabolites from T. pardinum as novel scaffolds for developing anticancer agents targeting PARP1 and PIP4K2γ.
Abstract
Natural products from fungi are a significant source for drug discovery. This study investigates six previously uncharacterized metabolites isolated from the poisonous mushroom Tricholoma pardinum using an integrated in silico approach to evaluate their therapeutic potential. Pharmacokinetic (ADMET) profiling predicted varied drug-likeness and toxicity profiles, with several compounds showing potential to cross the blood-brain barrier. Molecular docking and MM-GBSA calculations identified compound 1 as a potent inhibitor of Poly [ADP-ribose] polymerase 1 (PARP1), with a strong binding affinity (XP GScore: -6.756; ΔGbind: -48.75 kcal/mol). This interaction is anchored by a robust network of hydrogen bonds with key residues, including ASP914, CYS908, and THR866. Similarly, compound 6 emerged as a strong binder to Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma (PIP4K2γ) (XP GScore: -7.705; ΔGbind: -45.94 kcal/mol), with its binding stabilized by extensive hydrophobic interactions complemented by a critical hydrogen bond with the residue Methionine 206 (MET206). Subsequent 100 ns molecular dynamics simulations confirmed the high stability of both protein-ligand complexes, validating the persistence of these key interactions. These computational findings highlight the potential of metabolites from T. pardinum as novel scaffolds for developing anticancer agents targeting PARP1 and PIP4K2γ, warranting further experimental validation.
Findings suggest that S. levi metabolites, particularly 1-O-nonacosylglycerol, represent preliminary screening for managing postprandial glucose levels.
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The docking analysis suggest that selected N-(substituted-1,3-benzothiazol-2-yl)benzamide derivatives, particularly Cp1, Cp3, Cp7, Cp10, Cp12, Cp13, and Cp14 were identified as the most promising lead candidates, with significant potential for anticonvulsant activity.
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INTRODUCTION
Bletilla striata, a traditional Chinese medicinal herb, shows promise for treating bacterial infections, but its precise antibacterial mechanisms are not fully understood.
MATERIALS AND METHODS
An integrated strategy was employed. Network pharmacology identified bioactive compounds from Bletilla striata and predicted antibacterial targets. Molecular docking assessed interactions between key compounds and core targets (ESR1, EGFR, PTGS2, MAPK14), followed by molecular dynamics simulations for the top complex (BJ6-ESR1). In vitro assays evaluated the antibacterial activity, anti-persister effects, and potential for resistance induction of the key compound BJ6 against S. aureus and Gram-negative bacteria.
RESULTS
Nine bioactive compounds were identified. 4,7-dihydroxy-1-p-hydroxybenzyl-2-methoxy-9,10- dihydrophenanthrene (BJ6) showed the strongest binding to key targets in docking. MD simulations confirmed a stable BJ6-ESR1 complex with a high binding free energy of -39.98 kcal/mol. In vitro, BJ6 exhibited potent activity against S. aureus (MIC = 1~2 μg/mL), significant efficacy against persister cells, and a delayed development of bacterial resistance compared to amoxicillin.
DISCUSSION
The findings indicate that Bletilla striata, primarily through BJ6, exerts antibacterial effects via multi-component, multi-target interactions, particularly with ESR1, EGFR, PTGS2, and MAPK14.
CONCLUSION
This study elucidates the molecular basis of Bletilla striata's antibacterial activity, highlighting BJ6 as a key bioactive component.
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The genus Dendrobium is a rich source of bioactive secondary metabolites, particularly bibenzyl derivatives with substantial pharmacological activities, but Dendrobium stuartii remains an underexplored species. Therefore, this study aimed to investigate the drug discovery potential of D. stuartii through an integrated in silico and experimental method. Four key compounds were prioritized through literature analysis, and the interactions with the epidermal growth factor receptor (EGFR) were evaluated using molecular docking. The chemical profile of the acetone extract was characterized using Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS). Additionally, biological activities were assessed through antibacterial, antibiofilm, and anti-inflammatory assays. Batatasin III had the strongest predicted binding affinity toward EGFR, and the LC-HRMS analysis confirmed the presence of bibenzyl derivative 3,4ʹ-dihydroxy-5,5ʹ-dimethoxybibenzyl (gigantol). The extract provided antibacterial activity, specifically against S. aureus and P. acnes, inhibited biofilm formation during the mid-phase, and produced substantial anti-inflammatory activity, as evidenced by significant inhibition of protein denaturation. The results suggested D. stuartii as a promising underexplored source of bioactive compounds with potential applications in anticancer and anti-infective drug development.
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