Efficacy of the cyclooctadepsipeptide PF1022A againstHeligmosomoides bakeri in vitroandin vivo

Abstract

SUMMARYThe cyclooctadepsipeptide PF1022A derived from the fungus,Mycelia sterilia, is characterized by a broad spectrum of activity against different parasitic gastrointestinal nematodes of livestock. In the present work the anthelmintic activity of PF1022A againstHeligmosomoides bakeri, a widely used laboratory model was studied. Albendazole, ivermectin and levamisole served as reference.In vitro, PF1022A showed low activity on embryonation but significantly inhibited egg hatch (10 and 100μg/ml), whereas albendazole (10 and 100μg/ml) revealed statistically significant inhibitions of both embryonation and egg hatch. PF1022A (1–100μg/ml) completely inhibited larval movement at most examination points. Comparable significant anthelmintic activity on the larval stages ofH. bakeriwas observed with levamisole (48–100%), while slightly lower activities were observed with ivermectin (20–92%) and albendazole (0–87%) at 1–100μg/ml. PF1022A and levamisole significantly inhibited motility and egg release of adult worms, while albendazole and ivermectin failed to demonstrate activity. Significant worm burden reductions were achieved with PF1022A, levamisole and ivermectinin vivo. For example, at 0·125 mg/kg PF1022A a worm burden reduction of 91·8% was observed. The use of drug combinations did not further enhance thein vitroandin vivoactivity of PF1022A. In conclusion, further investigations are warranted with PF1022A, as the drug is characterized by significant larvicidal and nematocidal activityin vitroandin vivo.