Larvicidal and macrofilaricidal efficacy of closantel and morantel against mosquito larvae and Setaria digitata nematodes

Abstract

Vector-borne diseases are major public health problems in the growing world and insecticide resistance threatens the elimination programs. Repurposed drugs could be a solution to develop novel larvicides to combat growing insecticide resistance among mosquito vectors and novel macrofilaricides to eliminate lymphatic filariasis (LF). In the present study, two veterinary drugs, closantel, and morantel were assessed for larvicidal activity against three mosquito larvae and macrofilaricidal activity against Setaria digitata, a lymphatic filariasis model organism. The larvicidal activity was assessed with a bioassay against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus larvae with concentrations between 0.1 ppm and 10 ppm. The macrofilaricidal activity was assessed using worm motility and MTT assays against Setaria digitata nematodes with concentrations between 0.05 mg/mL to 0.001 mg/mL. Among the two drugs tested, closantel was found to be effective against An. stephensi, Cx. quinquefasciatus and Ae. aegypti larvae with LC₅₀ values of 0.183, 0.658, 0.773 ppm, and LC₉₀ values of 1.577, 2.560, 2.108, respectively. Both closantel and morantel demonstrated macrofilaricidal activity. However, morantel showed strong macrofilaricidal activity with 87.29 % and 87.49 % inhibition at 492 and 510 nm, respectively, in the MTT assay at the lowest concentration of 0.01 mg/mL. But closantel showed 85.26 % and 86.28 % inhibition at 492 and 510 nm, respectively, in the MTT assay at 0.05 mg/mL. These findings suggest that closantel and morantel could be promising candidates as repurposed drugs for larvicides and macrofilaricides and may provide valuable insights into effective target mechanisms against vector-borne diseases.