Biotransformation of wortmannilactone F (3) using the marine-derived fungus DL1103 generated wortmannilactone M (1), a novel analog of wortmannilactone, which was a reduction product of 3 at the C-3 carbonyl group. The in vitro inhibitory activities of 10 wortmannilactones, including 1, against electron transport enzymes indicated that all the wortmannilactones were selective inhibitors of NADH-fumarate reductase and NADH-rhodoquinone reductase. The structure-activity relationship analysis showed that the relative configuration of C1" and C5", the positions of double bonds, the oxygen atoms in the dihydropyran moiety, and the keto-carbonyl group in the oxabicyclo-[2.2.1]-heptane moiety were important to the inhibitory activity of wortmannilactones. In vivo studies indicated that 3 significantly decreased the number and size of adult worms in Trichinella spiralis-infected mice in a dose-dependent manner. Notable changes in the cuticle and microvilli of T. spiralis were also observed. Our data provided useful information in the research and development of polyketides with dihydropyran and oxabicyclo [2.2.1] heptane moieties as antihelminthics.

中文翻译：

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沃特曼内酯对蠕虫电子运输链酶的活性，构效关系以及对旋毛虫感染的小鼠的影响。

使用海洋衍生真菌DL1103对渥曼尼内酯F（3）进行生物转化，生成了渥曼尼内酯M（1），它是渥曼尼内酯的新型类似物，在C-3羰基上为3的还原产物。10种渥曼半乳糖内酯对电子转运酶的体外抑制活性表明，所有渥曼半乳糖内酯都是NADH-富马酸酯还原酶和NADH-Rhododoquinone还原酶的选择性抑制剂。结构-活性关系分析表明，C1”和C5”的相对构型，双键的位置，二氢吡喃部分中的氧原子以及氧杂环-[2.2.1]-庚烷部分中的酮羰基对渥曼青内酯的抑制活性很重要。体内研究表明，有3种剂量依赖性地显着减少了旋毛虫感染的小鼠中成虫的数量和大小。还观察到螺旋藻的表皮和微绒毛有显着变化。我们的数据为研究以二氢吡喃和氧杂双环[2.2.1]庚烷部分为抗蠕虫药的聚酮化合物提供了有用的信息。