Leibniz Institute for Natural Product Research and Infection Biology e.V. , Hans-Knöll-Institute , Beutenbergstraße 11a , 07745 Jena , Germany.
Chair of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy , Friedrich-Schiller-University , Philosophenweg 14 , 07743 Jena , Germany.
J Nat Prod. 2019 Sep 27;82(9):2544-2549. doi: 10.1021/acs.jnatprod.9b00403. Epub 2019 Aug 29.
Precursor-directed biosynthesis was used to introduce selected aryl carboxylic acids into the pseudochelin pathway, which had recently been assembled in . Overall, 14 previously undescribed analogues of the natural products myxochelin B and pseudochelin A were generated and structurally characterized. A subset of 10 derivatives together with their parental molecules were evaluated for their activity toward human 5-lipoxygenase. This testing revealed pseudochelin A as the most potent 5-lipoxygenase inhibitor among the naturally occurring compounds, whereas myxochelin A is the least active. Replacement of the catechol moieties in myxochelin B and pseudochelin A affected the bioactivity to different degrees.
采用前体定向生物合成的方法将选定的芳基羧酸引入最近在. 中组装的假壳素途径中。总体而言，生成并结构表征了天然产物粘菌素 B 和假壳素 A 的 14 种以前未描述的类似物。对一组 10 种衍生物及其母体分子进行了针对人 5-脂氧合酶活性的评估。测试表明，在天然化合物中，假壳素 A 是最有效的 5-脂氧合酶抑制剂，而粘菌素 A 的活性最低。粘菌素 B 和假壳素 A 中儿茶酚部分的替换在不同程度上影响了生物活性。
