ArticleBotanical studies2025
Novel inducible nitric oxide synthase-inhibiting cytochalasins from an oyster-derived fungus Westerdykella dispersa Ca4-13: structural insights and molecular docking analysis.
Article in Botanical studies, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Spiro-Linked Polyketides from Cultures ofJournal of natural products · 2026Article
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Abstract
backgroundMarine-derived microorganisms are renowned for producing structurally diverse secondary metabolites with notable biological activities, serving as a promising reservoir for pharmaceutical development. In this study, the fungal strain Westerdykella dispersa Ca4-13, isolated from the edible oyster Crassostrea angulata, was investigated for its potential anti-inflammatory and cytoprotective properties using BV-2 microglial cells as a model system.
resultsMetabolite profiling of the solid-state fermented products of W. dispersa Ca4-13 yielded seven compounds 1-7. Their structures were elucidated using NMR and MS techniques, revealing three previously undescribed cytochalasins, namely westerchalasin A (1), westerchalasin B (2), and westerchalasin C (3), along with four known compounds 4-7. Among these, westerchalasin B (2) and westerchalasin C (3) significantly exhibited nitric oxide (NO) production production in LPS-stimulated BV-2 microglial cells, with IC₅₀ values of 11.1 ± 0.4 and 9.9 ± 0.4 µM, respectively. Western blot analysis demonstrated that compounds 2 and 3 significantly downregulated inducible nitric oxide synthase (iNOS) expression at a concentration of 20 µM. Moreover, molecular docking analysis revealed that compound 3 exhibited a high binding affinity for iNOS synthase (ΔG = -18.8104 kcal/mol). The strong interaction was attributed to of hydrogen bonds between the catalytic residue Arg375 and the C-18 carbonyl group of the cycloundecene moiety, as well as Pi-alkyl interactions with Trp367, which contributed to enhanced stability of the complex.
conclusionsThis study reported the isolation and structural elucidation of three novel cytochalasins 1-3 from W. dispersa Ca4-13. Notably, compounds 2 and 3 demonstrated anti-inflammatory activity by inhibiting NO production and iNOS expression in LPS-stimulated BV-2 microglial cells. Molecular docking analysis further confirmed strong interactions between compound 3 and key iNOS residues. Given the crucial role of neuroinflammation in neurodegenerative disorders, these findings suggested that compounds 2 and 3 may possess dual neuroprotective properties, warranting further exploration for therapeutic applications.
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