title: Anthelmintic profile of the cyclodepsipeptide PF1022A in in vitro and in vivo models.
abstract: A novel cyclodepsipeptide of fungal origin, PF1022A, recently was reported to have anthelmintic activity. To supplement published reports and determine potential utility of PF1022A as a ruminant anthelmintic, the compound was examined in in vitro and in vivo models. Assays used measured motility of Haemonchus contortus (intrinsic drug potency), ATP levels (parasite death), and activity against H. contortus, Ostertagia ostertagi, and Trichostrongylus colubriformis in the jird (spectrum, potency, and efficacy by various routes). The potency of PF1022A in reducing motility is greater than commercial anthelmintics. Examination of ATP levels in PF1022A-paralyzed H. contortus indicates that worms are not killed, suggesting the compound acts as a neurotoxin in nematodes. In the jird, PF1022A has activity orally against each of the parasites studied and at doses comparable to all commercial anthelmintics, except the macrocyclic lactones which are more potent. Unfortunately, for some nematode species, parenteral delivery is ineffective at realistic doses.
authors.affiliation: Upjohn Laboratories, Kalamazoo, Michigan 49001, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Conder
authors.forename: S S
authors.initials: SS
authors.lastname: Johnson
authors.forename: D S
authors.initials: DS
authors.lastname: Nowakowski
authors.forename: T E
authors.initials: TE
authors.lastname: Blake
authors.forename: F E
authors.initials: FE
authors.lastname: Dutton
authors.forename: S J
authors.initials: SJ
authors.lastname: Nelson
authors.forename: E M
authors.initials: EM
authors.lastname: Thomas
authors.forename: J P
authors.initials: JP
authors.lastname: Davis
authors.forename: D P
authors.initials: DP
authors.lastname: Thompson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D047630:Depsipeptides; D005260:Female; D005849:Gerbillinae; D006188:Haemonchiasis / Q000188:drug therapy*; D006189:Haemonchus / Q000187:drug effects; D015394:Molecular Structure; D010028:Ostertagia / Q000187:drug effects; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D014254:Trichostrongylus / Q000187:drug effects
chemical_list: D000871:Anthelmintics; D047630:Depsipeptides; D010456:Peptides, Cyclic; C075544:PF 1022A; D000255:Adenosine Triphosphate