Departamento Sanidad Animal, Instituto de Ganadería de Montaña, CSIC-Universidad de León, Grulleros, 24346, León, Spain.
Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de León, Campus de Vegazana S/N, 24071, León, Spain.
Parasit Vectors. 2024 Apr 3;17(1):173. doi: 10.1186/s13071-024-06224-6.
Control of the zoonotic food-borne parasite Fasciola hepatica remains a major challenge in humans and livestock. It is estimated that annual economic losses due to fasciolosis can reach US$3.2 billion in agriculture and livestock. Moreover, the wide distribution of drug-resistant parasite populations and the absence of a vaccine threaten sustainable control, reinforcing the need for novel flukicides.
The present work analyses the flukicidal activity of a total of 70 benzimidazole derivatives on different stages of F. hepatica. With the aim to select the most potent ones, and screenings were first performed on eggs at decreasing concentrations ranging from 50 to 5 µM and then on adult worms at 10 µM. Only the most effective compounds were also evaluated using a resistant isolate of the parasite.
After the first screenings at 50 and 10 µM, four hit compounds (BZD31, BZD46, BZD56, and BZD59) were selected and progressed to the next assays. At 5 µM, all hit compounds showed ovicidal activities higher than 71% on the susceptible isolate, but only BZD31 remained considerably active (53%) when they were tested on an albendazol-resistant isolate, even with values superior to the reference drug, albendazole sulfoxide. On the other hand, BZD59 displayed a high motility inhibition when tested on adult worms from an albendazole-resistant isolate after 72 h of incubation.
BZD31 and BZD59 compounds could be promising candidates for the development of fasciolicidal compounds or as starting point for the new synthesis of structure-related compounds.
控制动物源性食源性寄生虫华支睾吸虫在人类和牲畜中仍然是一个主要挑战。据估计，华支睾吸虫病每年给农业和畜牧业造成的经济损失可达 32 亿美元。此外，耐药寄生虫种群的广泛分布和缺乏疫苗威胁着可持续控制，这加剧了对新型杀肝吸虫药物的需求。
本工作分析了总共 70 种苯并咪唑衍生物对不同阶段的华支睾吸虫的杀肝吸虫活性。为了选择最有效的化合物，首先在浓度从 50 到 5 μM 逐渐降低的情况下对卵进行筛选，然后在 10 μM 下对成虫进行筛选。只有最有效的化合物也用寄生虫的耐药分离株进行了评估。
在 50 和 10 μM 进行首次筛选后，选择了四种命中化合物（BZD31、BZD46、BZD56 和 BZD59）并进行了下一步的检测。在 5 μM 时，所有命中化合物对敏感分离株的杀卵活性均高于 71%，但当用阿苯达唑耐药分离株进行测试时，只有 BZD31 仍具有相当的活性（53%），甚至优于参考药物阿苯达唑亚砜。另一方面，BZD59 在孵育 72 小时后对阿苯达唑耐药分离株的成虫表现出较高的运动抑制活性。
BZD31 和 BZD59 化合物可能是开发杀肝吸虫化合物的有前途的候选药物，或者作为结构相关化合物新合成的起点。
