Novel inducible nitric oxide synthase-inhibiting cytochalasins from an oyster-derived fungus Westerdykella dispersa Ca4-13: structural insights and molecular docking analysis
Journal
Botanical Studies
Journal Volume
66
Journal Issue
1
Start Page
Article number: 33
ISSN
1999-3110
Date Issued
2025-10-07
Author(s)
Abstract
Background
Marine-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.
Results
Metabolite 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.
Conclusions
This 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.
Subjects
Anti‑inflammation
Molecular docking
Sporormiaceae
Westerchalasin
Westerdykella dispersa
Publisher
Springer Science and Business Media LLC
Type
journal article