Benzimidazole and aminoalcohol derivatives show in vitro anthelmintic activity against Trichuris muris and Heligmosomoides polygyrus
Elora Valderas-García, Cécile Häberli, María Álvarez Bardón, Nerea Escala, Verónica Castilla Gómez de Agüero, Jennifer de la Vega, Esther del Olmo, Rafael Balaña‐Fouce, Jennifer Keiser, María Martínez Valladares
Abstract
Abstract Background 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. Methods 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 1 motility by > 90% at a single concentration of 100 µM; then, their respective IC 50 values were calculated. Those compounds with IC 50 < 10 µM were also tested against the adult stage of T. muris and H. polygyrus at a single concentration of 10 µM. Results Of the 41 initial compounds screened, only compounds AO14, BZ6 and BZ12 had IC 50 values < 10 µM on T. muris L 1 assay, showing IC 50 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 50 of 8.1 µM) and 53% of H. polygyrus while BZ6 killed 100% of H. polygyrus adults (IC 50 of 5.3 µM) but only 17% of T. muris. Conclusions BZ6 and BZ12 could be considered as a starting point for the synthesis of further structurally related compounds. Graphical Abstract