Instituto de Ganadería de Montaña, CSIC-Universidad de León, 24346, Grulleros, León, Spain.
Departamento de Ciencias Biomédicas, Facultad de Veterinaria, Universidad de León, 24071, León, Spain.
Parasit Vectors. 2022 Jul 8;15(1):243. doi: 10.1186/s13071-022-05347-y.
Infections by gastrointestinal nematodes cause significant economic losses and disease in both humans and animals worldwide. The discovery of novel anthelmintic drugs is crucial for maintaining control of these parasitic infections.
For this purpose, the aim of the present study was to evaluate the potential anthelmintic activity of three series of compounds against the gastrointestinal nematodes Trichuris muris and Heligmosomoides polygyrus in vitro. The compounds tested were derivatives of benzimidazole, lipidic aminoalcohols and diamines. A primary screening was performed to select those compounds with an ability to inhibit T. muris L motility by > 90% at a single concentration of 100 µM; then, their respective IC values were calculated. Those compounds with IC < 10 µM were also tested against the adult stage of T. muris and H. polygyrus at a single concentration of 10 µM.
Of the 41 initial compounds screened, only compounds AO14, BZ6 and BZ12 had IC values < 10 µM on T. muris L assay, showing IC values of 3.30, 8.89 and 4.17 µM, respectively. However, only two of them displayed activity against the adult stage of the parasites: BZ12 killed 81% of adults of T. muris (IC of 8.1 µM) and 53% of H. polygyrus while BZ6 killed 100% of H. polygyrus adults (IC of 5.3 µM) but only 17% of T. muris.
BZ6 and BZ12 could be considered as a starting point for the synthesis of further structurally related compounds.
胃肠道线虫感染在全球范围内给人类和动物造成了重大的经济损失和疾病。发现新的驱虫药物对于控制这些寄生虫感染至关重要。
为此，本研究旨在评估 3 个系列化合物对体外胃肠道线虫秀丽隐杆线虫和旋毛虫的潜在驱虫活性。测试的化合物为苯并咪唑衍生物、脂基氨基酸醇和二胺。进行了初步筛选，以选择那些在 100μM 单一浓度下能抑制秀丽隐杆线虫 L 运动超过 90%的化合物；然后计算它们各自的 IC 值。那些 IC 值<10μM 的化合物也在 10μM 的单一浓度下测试对成熟阶段的秀丽隐杆线虫和旋毛虫的作用。
在最初筛选的 41 种化合物中，只有化合物 AO14、BZ6 和 BZ12 在秀丽隐杆线虫 L 试验中具有 IC 值<10μM，其 IC 值分别为 3.30、8.89 和 4.17μM。然而，只有其中两种对寄生虫的成虫阶段显示出活性：BZ12 杀死了 81%的秀丽隐杆线虫成虫（IC 值为 8.1μM）和 53%的旋毛虫，而 BZ6 杀死了 100%的旋毛虫成虫（IC 值为 5.3μM），但仅杀死了 17%的秀丽隐杆线虫。
BZ6 和 BZ12 可以被认为是进一步合成结构相关化合物的起点。
