Huiping Yu, Xuejing Hao, Yungeng Gao, Lin Yang, Yao Qin, Xiaoqing Li, Yan-Long Yang
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Precursor-Directed Biosynthesis of Panepoxydone Derivatives with Nitric Oxide Production Inhibitory Activity.
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.
期刊介绍:
ChemBioChem (Impact Factor 2018: 2.641) publishes important breakthroughs across all areas at the interface of chemistry and biology, including the fields of chemical biology, bioorganic chemistry, bioinorganic chemistry, synthetic biology, biocatalysis, bionanotechnology, and biomaterials. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and supported by the Asian Chemical Editorial Society (ACES).