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.
Abstract:
Panepoxydone is a natural NF-κB inhibitor isolated from basidiomycetes belonging to the genus Panus and Lentinus. It is biosynthesized from prenylhydroquinone through successive hydroxylation, epoxidation, and reduction reactions. In this study, we establish an efficient precursor-directed biosynthesis strategy for the structural expansion of panepoxydone based on its biosynthetic pathway. Supplementation of the panepoxydone-producing strain, Panus rudis, with various prenylhydroquinone analogues enabled the production of fourteen previously undescribed panepoxydone derivatives, panepoxyquinoid A-N (2-14). The obtained panepoxydone derivatives together with their parental molecules were evaluated for their inhibitory activity on LPS-induced NO production in RAW 264.7 cells. Compounds 1, 5-6, 10-11, and 14-15 displayed significant suppressive effects on LPS-induced NO production with IC50 values ranging from 4.3 to 30.1 μM.
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