Jietacins, an azoxy antibiotic class of chemicals, were isolated from the culture broth of Streptomyces sp. KP-197. They have a unique structural motif, including a vinyl azoxy group and a long acyclic aliphatic chain, which is usually branched but non-branched in the case of jietacin C. During a drug discovery program, we found that jietacins display potent anthelmintic activity against parasitic nematodes and that jietacin A has a moderate or low acute toxicity (LD₅₀ > 300 mg/kg) and no mutagenic potential in a mini Ames screen. This suggests that jietacins have potential for drug discovery research. In order to create a novel anthelmintic agent, we performed design, synthesis, and biological evaluation of jietacin derivatives against parasitic nematodes. Of these derivatives, we found that a fully synthesized simplified derivative exhibited better anthelmintic activity against three parasitic nematodes than natural jietacins. In addition, it had a better efficacy in vivo through oral administration against a mouse nematode. This indicated that the azoxy motif could prove useful as a template for anthelmintic discovery, possibly creating a class of anthelmintic with novel skeletons, a potential new mode of action, and providing further insight for rational drug design.

从链霉菌属（Streptomyces sp。）的培养液中分离出杰他霉素（一种抗氧化抗生素类化学品）。KP-197。它们具有独特的结构基序，包括乙烯基叠氮基和较长的无环脂族链，在杰他霉素C的情况下通常是分支但非分支的。在药物发现计划中，我们发现杰他霉素显示出有效的驱虫活性，可对抗寄生虫。线虫，认为捷他霉素A具有中等或低急性毒性（LD ₅₀ > 300 mg / kg），并且在小型Ames筛选中没有诱变潜能。这表明节他霉素具有用于药物发现研究的潜力。为了创建一种新型的驱虫药，我们进行了针对寄生线虫的节他霉素衍生物的设计，合成和生物学评估。在这些衍生物中，我们发现完全合成的简化衍生物比天然洁他霉素对三种寄生线虫表现出更好的驱虫活性。另外，它通过口服给药对抗小鼠线虫在体内具有更好的功效。这表明，偶氮基序可能被证明可以作为驱虫药发现的模板，可能创建一类具有新颖骨架，潜在的新作用方式的驱虫药，并为合理的药物设计提供进一步的见解。