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 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 L₁ motility by > 90% at a single concentration of 100 µM; then, their respective IC₅₀ values were calculated. Those compounds with IC₅₀ < 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 IC₅₀ values < 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 a starting point for the synthesis of further structurally related compounds.

Keywords: Aminoalcohol; Anthelmintic; Benzimidazole; Diamine; Heligmosomoides polygyrus; Trichuris muris.