title: Efficacy of the cyclooctadepsipeptide PF1022A against Heligmosomoides bakeri in vitro and in vivo.
abstract: The 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 against Heligmosomoides 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 100 μg/ml), whereas albendazole (10 and 100 μg/ml) revealed statistically significant inhibitions of both embryonation and egg hatch. PF1022A (1-100 μg/ml) completely inhibited larval movement at most examination points. Comparable significant anthelmintic activity on the larval stages of H. bakeri was observed with levamisole (48-100%), while slightly lower activities were observed with ivermectin (20-92%) and albendazole (0-87%) at 1-100 μg/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 ivermectin in 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 the in vitro and in vivo activity of PF1022A. In conclusion, further investigations are warranted with PF1022A, as the drug is characterized by significant larvicidal and nematocidal activity in vitro and in vivo.
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P.O. Box, CH-4002 Basel, Switzerland.
authors.forename: Uzoma
authors.initials: U
authors.lastname: Nwosu
authors.forename: Mireille
authors.initials: M
authors.lastname: Vargas
authors.forename: Achim
authors.initials: A
authors.lastname: Harder
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keiser
mesh_terms: D015766:Albendazole / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D047630:Depsipeptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004338:Drug Combinations; D005243:Feces / Q000469:parasitology; D005260:Female; D006369:Heligmosomatoidea / Q000187:drug effects* / Q000254:growth & development; D007559:Ivermectin / Q000494:pharmacology; D007814:Larva / Q000187:drug effects* / Q000254:growth & development; D007978:Levamisole / Q000494:pharmacology; D058751:Livestock / Q000469:parasitology; D051379:Mice; D008815:Mice, Inbred Strains; D010270:Parasite Egg Count; D017206:Strongylida Infections / Q000188:drug therapy* / Q000469:parasitology; D016896:Treatment Outcome
chemical_list: D000871:Anthelmintics; D047630:Depsipeptides; D004338:Drug Combinations; C075544:PF 1022A; D007978:Levamisole; D007559:Ivermectin; D015766:Albendazole