Additive larvicidal activity of albendazole combined with a hydroxyethylamine-derived compound against Toxocara canis larvae: An in vitro and in silico study.

Abstract

Human toxocariasis is a neglected zoonotic helminthiasis characterized by larval migration through tissues such as the liver, lungs, central nervous system, and eyes. Current pharmacological treatment presents variable efficacy, highlighting the need for improved therapeutic strategies. This study evaluated the larvicidal activity of albendazole combined with heteroaromatic sulfonamide compounds derived from hydroxyethylamine against Toxocara canis, using in vitro assays, in silico analyses, and a checkerboard design. Three synthetic compounds were initially screened for larvicidal activity and cytotoxicity. All induced 100% larval unviability at 1 mg/mL; however, only HIDROXI 1 maintained complete larvicidal activity at 0.5 mg/mL, while exhibiting an acceptable cytotoxicity profile. In silico analyses indicated physicochemical properties consistent with favorable oral bioavailability and compliance with Lipinski's Rule of Five. Albendazole alone induced complete larval unviability only at 40 mg/mL. In the checkerboard assay, the combination of HIDROXI 1 (0.25 mg/mL) with albendazole (10 or 5 mg/mL) resulted in 100% and 99% larval unviability, respectively, indicating an additive interaction. These findings indicate that HIDROXI 1 exhibits promising in vitro larvicidal activity and may enhance the effect of albendazole at lower concentrations, supporting further investigation of this combination as a potential therapeutic approach for toxocariasis.