Heterocornols from the Sponge-Derived Fungus Pestalotiopsis heterocornis with Anti-Inflammatory Activity.
Hui LeiXiaoxu BiXiuping LinJianglian SheXiao-Wei LuoHong NiuDan ZhangBin YangPublished in: Marine drugs (2021)
One strain-many compounds (OSMAC) manipulation of the sponge-derived fungus Pestalotiopsis heterocornis XWS03F09 resulted in the production of new secondary metabolites. The chemical study of the fermentation, cultivated on 3% artificial sea salt in the rice media, led to the isolation of twelve compounds, including eight new polyketide derivatives, heterocornols Q-X (1-8), one new ceramide (9), and three known analogues (10-12). The structures and absolute configurations of the new compounds were elucidated by spectroscopic data and calculated ECD analysis. Heterocornols Q (1) and R (2) are novel 6/5/7/5 tetracyclic polyketide derivatives featuring dihydroisobenzofuran and benzo-fused dioxabicyclo [4.2.1] nonane system, which might be derived from the acetyl-CoA by epoxidation, polyene cyclization, and rearrangement to form the core skeleton. Compound 12 showed moderate or weak antimicrobial activities against with MIC values ranging from 25 to 100 μg/mL. Heterocornols T and X (7 and 8) could inhibit the production of LPS-induced NO significantly, comparable to dexamethasone. Further Western blotting analysis showed 7 and 8 markedly suppressed the iNOS protein expression in LPS-induced RAW 264.7 cells in a dose-dependent manner. The result showed that 7 and 8 might serve as potential leads for development of anti-inflammatory activity.
Keyphrases
- lps induced
- inflammatory response
- molecular docking
- induced apoptosis
- staphylococcus aureus
- low dose
- high resolution
- electronic health record
- south africa
- oxidative stress
- risk assessment
- high intensity
- fatty acid
- machine learning
- cell cycle arrest
- cell proliferation
- endoplasmic reticulum stress
- artificial intelligence
- big data
- nitric oxide synthase
- human health
- lactic acid