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. Graphical Abstract

New benzimidazole derivative compounds with in vitro fasciolicidal properties

“…The results of that study showed that BZD9 was the most effective compound, displaying a 50% inhibitory concentration (IC 50 ) value of 6 µM in eggs by the EHT [ 20 ]. Some of these compounds were also evaluated in two rodent models of other gastrointestinal nematodes, demonstrating that BZD09 effectively inhibited the motility of Heligmosomoides polygyrus adults at a concentration of 10 µM, while BZD15 inhibited Trichuris muris adult motility at the same concentration [ 54 ]. However, in the current study, none of these compounds exhibited activities exceeding 25% when tested against F. hepatica eggs at a concentration of 50 µM.…”

Molecular dynamics and NMR reveal the coexistence of H-bond-assisted and through-space JFH coupling in fluorinated amino alcohols

“…Amino alcohols are functional groups commonly found in molecules associated with a range of biological activities. These include antimalarial, 22 anthelmintic, 23 cardioprotective, 24 antifungal 25 and antioxidative activities in vitro . 26 Moreover, these compounds have demonstrated in vitro antitumor potential, 27 the ability to inhibit human carbonic anhydrases, 28 antiproliferative activity against cervical, breast, and ovary cancer cells, 29 and potential in treating genetic diseases.…”

Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review

“…Among these heterocycles, benzimidazole stands out, as a purine-analog pharmacophore, with a very diverse therapeutic activity. The very broad spectrum of biological activities it treats include antimicrobial [4][5][6][7][8], antiviral [9,10], antihistamine [11,12], anticonvulsant [3,13], antitumor [14][15][16], proton pump inhibitors [17], antiparasitic [16,18,19], anti-inflammatory [20][21][22], or antihypertensive [23,24] activities. Some benzimidazoles are efficient agents in Diabetes mellitus [25][26][27], while astemizole compounds possess anti-prion activity to treat Creutzfeldt-Jakob disease [5,28].…”