受粘球霉素启发的5-脂氧合酶抑制剂：合成与生物学评价
Myxochelin-Inspired 5-Lipoxygenase Inhibitors: Synthesis and Biological Evaluation.
作者信息
Schieferdecker Sebastian, König Stefanie, Pace Simona, Werz Oliver, Nett Markus
机构信息
Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Strasse 23, 07745, Jena, Germany.
Chair of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743, Jena, Germany.
出版信息
ChemMedChem. 2017 Jan 5;12(1):23-27. doi: 10.1002/cmdc.201600536. Epub 2016 Nov 29.
A total of 48 analogues of the natural product myxochelin A were prepared and evaluated for their inhibitory effects on human 5-lipoxygenase in both cell-free and cell-based assays. Structure-activity relationship analysis revealed that the secondary alcohol function and only chiral center of myxochelin A is not required for biological activity. By expanding the diaminoalkane linker of the two aromatic residues it was possible to generate a myxochelin derivative with superior activity against 5-lipoxygenase in intact cells.
总共制备了48种天然产物粘菌素A的类似物，并在无细胞和基于细胞的试验中评估了它们对人5-脂氧合酶的抑制作用。构效关系分析表明，粘菌素A的仲醇官能团和唯一的手性中心对生物活性并非必需。通过扩展两个芳香族残基的二氨基烷烃连接基，有可能生成一种在完整细胞中对5-脂氧合酶具有更高活性的粘菌素衍生物。
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