Precursor-Directed Biosynthesis of Panepoxydone Derivatives with Nitric Oxide Production Inhibitory Activity
Huiping Yu1, Xuejing Hao1, Yungeng Gao1
1State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou, 730000, P. R. China.
Chembiochem : a European Journal of Chemical Biology
|October 22, 2024
Summary
Researchers developed a new biosynthesis strategy to create novel panepoxydone derivatives from fungi. Fourteen new compounds were synthesized and tested, with several showing significant inhibitory effects on nitric oxide production.
Area of Science:
- Natural Product Chemistry
- Biosynthesis
- Medicinal Chemistry
Background:
- Panepoxydone is a natural NF-κB inhibitor derived from basidiomycetes.
- Its biosynthesis involves prenylhydroquinone through hydroxylation, epoxidation, and reduction.
- NF-κB inhibition is crucial for regulating inflammatory responses.
Purpose of the Study:
- To establish an efficient precursor-directed biosynthesis strategy for structural expansion of panepoxydone.
- To synthesize novel panepoxydone derivatives using prenylhydroquinone analogues.
- To evaluate the anti-inflammatory potential of these new compounds.
Main Methods:
- Precursor-directed biosynthesis using the fungus Panus rudis.
- Supplementation of the culture medium with prenylhydroquinone analogues.
- Isolation and structural elucidation of fourteen new panepoxydone derivatives (panepoxyquinoid A-N).
- In vitro evaluation of inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells.
Main Results:
- Fourteen novel panepoxydone derivatives (compounds 2-14) were successfully synthesized.
- Compounds 1, 5-6, 10-11, and 14-15 demonstrated significant suppression of LPS-induced NO production.
- The IC50 values for these active compounds ranged from 4.3 to 30.1 μM.
Conclusions:
- The developed precursor-directed biosynthesis strategy is effective for generating diverse panepoxydone analogues.
- Several novel panepoxydone derivatives exhibit potent inhibitory activity against nitric oxide production, suggesting potential anti-inflammatory properties.
- These findings open avenues for developing new therapeutic agents targeting inflammatory pathways.
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