Liu Guang-Lu, Hu Yang, Chen Xiao-Hui, Wang Gao-Xue, Ling Fei
College of Science, Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi 712100, China.
College of Animal Science and Technology, Northwest A&F University, Xinong Road 22nd, Yangling, Shaanxi 712100, China.
Bioorg Med Chem Lett. 2016 Oct 15;26(20):5039-5043. doi: 10.1016/j.bmcl.2016.08.090. Epub 2016 Aug 30.
With an intention to find more potent anti-parasite agents, four bromoalkane substituted coumarin derivatives (1-4) and twenty coumarin-imidazole hybrid derivatives were synthesized and screened for their anthelmintic activity and the acute toxicity. Anti-parasites results confirmed that most coumarin derivatives retained their anthelmintic activity against Dactylogyrus intermedius at the dose range from 1 to 10mg/L. Among the candidates, compound 23 showed the best anthelmintic activity than other compounds against D. intermedius infestation with EC value of 0.85mg/L. The structure-activity relationship analysis confirmed that the anthelmintic activities of derivatives were determined by the length of 'linker' (Rsubstitute position) and the substitute group in R position. The active data confirmed that six carbon atoms length of 'linker' and benzimidazole substitute group can increased the anthelmintic activity of compound, significantly. On the basis of these results, compound 23 can be used as a potential lead compound for the development of commercial drug against D. intermedius.
为了寻找更有效的抗寄生虫剂，合成了四种溴代烷烃取代的香豆素衍生物（1-4）和二十种香豆素-咪唑杂化衍生物，并对它们的驱虫活性和急性毒性进行了筛选。抗寄生虫结果证实，大多数香豆素衍生物在1至10mg/L的剂量范围内对中间指环虫仍保留其驱虫活性。在这些候选物中，化合物23对中间指环虫感染表现出比其他化合物更好的驱虫活性，其EC值为0.85mg/L。构效关系分析证实，衍生物的驱虫活性由“连接基”的长度（R取代位置）和R位置的取代基团决定。活性数据证实，六个碳原子长度的“连接基”和苯并咪唑取代基团可显著提高化合物的驱虫活性。基于这些结果，化合物23可作为开发抗中间指环虫商业药物的潜在先导化合物。
