Synthesis and anthelmintic activity of arctigenin derivatives against Dactylogyrus intermedius in goldfish
Synthesis and anthelmintic activity of arctigenin derivatives against Dactylogyrus intermedius in goldfish
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牛蒡甙元衍生物的合成及其对金鱼中间指环虫的驱虫活性
DOI：
10.1016/j.bmcl.2017.06.023
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发表时间：
2017
影响因子：
2.7
通讯作者：
Ling Fei
中科院分区：
文献类型：
--
作者：
Hu Yang;Liu Lei;Liu Guang-Lu;Tu Xiao;Wang Gao-Xue;Ling Fei
为了防治中间指环虫寄生虫病，本研究设计、合成并测试了一系列新的牛蒡甙元衍生物。大多数衍生物的驱虫活性范围为 1 至 10 mg/L。与传统药物吡喹酮（EC50=2.69mg/L）相比，醚衍生物2g和2he表现出略高的抗寄生虫活性，EC50值分别为2.48和1.52mg/L。此外，牛蒡苷元-咪唑杂合体4a和4b也去除了D。中间有效，EC50 值分别为 2.13 和 2.07 mg/L。构效关系分析表明，四个碳原子长度的连接基和咪唑取代基可显着提高驱虫活性，并降低毒性。通过扫描电镜观察，化合物4a和4b引起了D．中间皮层损伤，如密集的皱纹、孔洞和结节结构。总体而言，牛蒡甙元的结构优化分析表明4a和4b可用于预防和控制指环菌感染，并被认为是有前途的商业药物开发的先导化合物。
To control the parasitic disease ofDactylogyrusintermedius, a series of new arctigenin derivatives were designed, synthesized and tested in our study. The anthelmintic activity of most of the derivatives ranged from 1 to 10 mg/L. Compared to traditional drug praziquantel (EC50= 2.69 mg/L), ether derivatives2gand2hexhibited slightly higher anti-parasitic activity, with the EC50values of 2.48 and 1.52 mg/L, respectively. Furthermore, the arctigenin-imidazole hybrids4aand4balso removedD. intermediuseffectively, with the EC50values of 2.13 and 2.07 mg/L, respectively. The structure-activity relationship analysis indicated that four carbon atoms length of linker and imidazole substitute group could significantly increase the anthelmintic activity, and reduced the toxicity. Through the scanning electron microscope observation, compounds4aand4bcaused theD. intermediustegumental damage such as intensive wrinkles, holes and nodular structures. Overall, the structural optimization analysis of arctigenin suggested that4aand4bcan be used for preventing and controllingDactylogyrusinfections and considered as promising lead compounds for the development of commercial drugs.