Benzimidazole and aminoalcohol derivatives show in vitro anthelmintic activity against Trichuris muris and Heligmosomoides polygyrus

Abstract

Background: Infections by gastrointestinal nematodes cause significant economic losses and disease in both human 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 L1 motility by more than 90% at a single concentration of 100 µM, and then, their respective IC50 values were calculated. Those compounds with IC50 lower than 10 µM were also tested against the adult stage of T. muris and H. polygyrus at a single concentration of 10µM. Results: Of the 41 initial compounds screened, only compounds AO14, BZ6 and BZ12 had IC50 values lower than 10 µM on T. muris L1 assay, showing IC50 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 (IC50 of 8.1 µM) and 53% of H. polygyrus while BZ6 killed 100% of H. polygyrus adults (IC50 of 5.3 µM) but only 17% of T. muris. Conclusions: BZ6 and BZ12 could be considered as potential candidates for further in vivo efficacy testing.