Anthelmintic activity of aminoalcohol and diamine derivatives against the gastrointestinal nematode Teladorsagia circumcincta
2021
Valderas-García, Elora | de la Vega, Jennifer | Álvarez Bardón, María | Castilla Gómez de Agüero, Verónica | Escarcena, Ricardo | López-Pérez, José Luis | Rojo Vázquez, Francisco A. | San Feliciano, Arturo | del Olmo, Esther | Balaña-Fouce, Rafael | Martínez-Valladares, María
Gastrointestinal nematodes (GIN) infections are a serious problem in livestock production due to the great economic losses they cause. Their control is increasingly difficult because of the rapid development of drug resistance and the limited number of available drugs. Therefore, this study evaluated 18 aminoalcohol and 16 diamine derivatives against eggs, first and third stage larvae from a susceptible and a resistant isolate of Teladorsagia circumcincta collected from sheep. The effectiveness of the in vitro anthelmintic activity of the compounds was evaluated using three different procedures: Egg Hatch Test (EHT), Larval Mortality Test (LMT) and Larval Migration Inhibition Test (LMIT). Those compounds with activities higher than 90 % in the initial screening at 50 μM were selected to determine their half maximal effective concentration (EC₅₀). In parallel, cytotoxicity assays were conducted on Caco2 and HepG2 cell lines to calculate Selectivity Indexes (SI) for each compound. The diamine 30 presented the best results in preventing egg hatching, displaying the lowest EC₅₀ value (1.01 ± 0.04 μM) of all compounds tested and the highest SI (21.21 vs. Caco-2 cells). For the LMIT, the diamine 34 showed the highest efficacy, with EC₅₀ values of 2.67 ± 0.08 and 3.02 ± 0.09 μM on the susceptible and resistant isolate of the parasite, respectively.
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