2026-09-15T18:19:07Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1687442026-01-15T01:01:18Zcom_10366_149436com_10366_3947com_10366_3946com_10366_3823col_10366_151253

Escala, Nerea Valderas-García, Elora Bardón, María Álvarez Gómez de Agüero, Verónica Castilla Escarcena, Ricardo López-Pérez, José Luis Rojo-Vázquez, Francisco A San Feliciano, Arturo Balaña-Fouce, Rafael Martínez-Valladares, María Rojo-Vázquez, Francisco A. Olmo Fernández, Esther del 2026-01-14T09:22:36Z 2026-01-14T09:22:36Z 2020-12-15 2099-12-31 0223-5234 http://hdl.handle.net/10366/168744 10.1016/j.ejmech.2020.112554 32971409 1768-3254 Gastrointestinal nematode infections are the main diseases in herds of small ruminants. Resistance to the main established drugs has become a worldwide problem. The purpose of this study is to obtain and evaluate the in vitro ovicidal and larvicidal activity of some 2-phenylbenzimidazole derivatives on susceptible and resistant strains of Teladorsagia circumcincta. Compounds were prepared by known procedures from substituted o-phenylenediamines and arylaldehydes or intermediate sodium 1-hydroxyphenylmethanesulfonate derivatives. Egg Hatch Test (EHT), Larval Mortality Test (LMT) and Larval Migration Inhibition Test (LMIT) were used in the initial screening of compounds at 50 μM concentration, and EC50 values were determined for the most potent compounds. Cytotoxicity evaluation of compounds was conducted on human Caco-2 and HepG2 cell lines to calculate their Selectivity Indexes (SI). At 50 μM concentration, nine out of twenty-four compounds displayed more than 98% ovicidal activity on a susceptible strain, and four of them showed more than 86% on one resistant strain. The most potent ovicidal benzimidazole (BZ) 3 showed EC50 = 6.30 μM, for the susceptible strain, while BZ 2 showed the lowest EC50 value of 14.5 μM for the resistant strain. Docking studies of most potent compounds in a modelled Teladorsagia tubulin indicated an inverted orientation for BZ 1 in the colchicine binding site, probably due to its fair interaction with glutamic acid at codon 198, which could justify its inactivity against the resistant strain of T. circumcincta. MINECO: RETOS (AGL2016-79813-C2-1R/2R) Junta de Castilla y León co-financed by FEDER, UE (LE020P17) eng Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/embargoedAccess 2-Phenyl-1H-benzimidazoles; Cytotoxicity; Teladorsagia circumcincta; Tubulin docking studies; in vitro assays. Binding Sites Trichostrongyloidea Larva Humans Cell Line Molecular Docking Simulation Benzimidazoles Helminth Proteins Tubulin Animals Antinematodal Agents Ovum Protein Binding Compuesto orgánico, Materia orgánica, Oarasitologia, Enfermedad transmisible, larva Trichostrongyloidea proteínas de helmintos humanos línea celular unión proteica sitios de unión simulación de acoplamiento molecular óvulo tubulina (proteína) animales antinematodos bencimidazoles Synthesis, bioevaluation and docking studies of some 2-phenyl-1H-benzimidazole derivatives as anthelminthic agents against the nematode Teladorsagia circumcincta. info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion MINECO: RETOS (AGL2016-79813-C2-1R/2R). Junta de Castilla y León co-financed by FEDER, UE (LE020P17) European Journal of Medicinal Chemistry 208 112554