Computational prediction and docking studies of bioactive metabolites from grass-derived endophytic fungi

Molecular Networking-Guided Discovery of New Calbistrins from Aspergillus japonicus and Integrated Omics Analyses of Their Phytotoxic Mechanism

Fungal species are a rich source of bioactive metabolites for agrochemical discovery. LC-MS/MS-guided molecular networking of Aspergillus japonicus led to the isolation of eight rare calbistrin-type polyketides (1–8), including three new derivatives, japonidienes J–L (1–3). Their structures were elucidated by spectroscopic analysis and computational methods. Compounds 1, 2, and 5–8 were evaluated for phytotoxicity against Eleusine indica and Amaranthus retroflexus seeds. Compounds 1 and 2 inhibited E. indica radicle elongation by 89.4% and 87.8%, respectively, comparable to glyphosate, while compounds 1, 2, and 5 inhibited A. retroflexus seedling growth more strongly than glyphosate. Integrated omics, qRT-PCR, and molecular docking/molecular dynamics simulations analyses suggested that compound 1 may affect trehalose-related metabolism through potential interaction with trehalose-6-phosphate synthase. Zebrafish embryo assays indicated relatively low developmental toxicity, supporting calbistrins as promising herbicidal leads.

Identification of Potential Drug Leads from Dendrobium stuartii Through Integrated In Silico, Phytochemical, and Pharmacological Methods

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.

Identification of Bioactive Phytoconstituents from Michelia champaca L. Flowers and Their Interactions with CXCR4 and PTEN Targets: A Comprehensive ADMET,Molecular Docking, and Molecular Dynamics Study

P predictive findings suggest that specific M. champaca flower constituents possess strong targeted binding potential against PTEN and CXCR4 nodes, establishing a validated computational foundation that warrants downstream in vitro and in vivo functional experimental validation.

In Silico Docking Analysis of Phaleria macrocarpa Fruit Phytochemicals in Inhibiting SARS-CoV-2

SARS-CoV-2 has caused significant global mortality, and while synthetic antivirals are used, their potential side effects highlight the need for safer natural alternatives. Phaleria macrocarpa contains antiviral flavonoids but remains underexplored against SARS-CoV-2. This study aimed to identify phytochemicals in P. macrocarpa fruit using GC-MS and phytochemical screening, evaluate their antiviral potential to inhibit SARS-CoV-2 through in silico docking, and assess their pharmacokinetic properties via SwissADME. Extraction was performed using maceration, followed by screening and GC-MS, which revealed flavonoids, terpenoids, phenolics, sterols, glycosides, and seven compounds, with only squalene showing antiviral activity. Thirteen compounds from databases were further analysed, yielding binding affinities ranging from -5.5 to -8.6 kcal/mol. Among these, sesamin, Mahkoside A, and Mahkoside B exhibited the strongest predicted binding interactions. These findings suggest P. macrocarpa phytochemicals may serve as natural alternatives to existing antiviral treatments, warranting further experimental validation.

“Edible plant-associated fungal endophytes as sources of bioactive specialized metabolites: antimicrobial and docking insights”

Resorcylic Acid Lactones and Isocoumarin Derivatives from the Marine-Associated Polar Fungus Penicillium sp. OUCMDZ-4014

Marine-associated polar fungi are promising sources of structurally diverse natural products. To investigate polyketide metabolites from the Antarctic moss-derived fungus Penicillium sp. OUCMDZ-4014, HSQC NMR combined with DeepSAT analysis was used to prioritize fractions enriched in cyclic and aromatic polyketides, and chromane-like metabolites. Chromatographic separation yielded ten resorcylic acid lactone-derived aromatic polyketides, including RAL macrolides, ring-opened esters, and isocoumarins, among which compounds 4–7 were new. Their planar structures were established by HRESIMS and 1D/2D NMR analyses. Their chemical structures including configurations were established by HRESIMS, 1D/2D NMR, ECD calculations, 13C NMR calculations, and DP4+ analysis. Isocoumarins 7–10 displayed diverse levels of α-glucosidase inhibition, with compound 9 being the most active (IC50 = 47.0 ± 3.83 μM). Kinetic analysis indicated noncompetitive inhibition by 9 and mixed-type inhibition by 10. Genome mining revealed a putative res biosynthetic gene cluster containing HR-PKS, NR-PKS, and tailoring-enzyme genes. Compound 1 underwent nonenzymatic conversion into 9 under culture-medium conditions, while trace conversion was also observed during concentration, revealing a chemical link between the RAL macrolide and isocoumarin scaffolds, and highlighting the contribution of post-biosynthetic chemical transformation to fungal polyketide diversification.