title: Anthelmintic activity of dioxapyrrolomycin.
abstract: Dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 produced by UC 11065 were evaluated as anthelmintics. Assays used to examine these compounds included effects on the free-living nematode Caenorhabditis elegans, ability to clear target nematodes (Haemonchus contortus and Trichostrongylus colubriformis) from jirds, and clearance of Haemonchus contortus from lambs. A crude extract of UC 11065 containing dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 was active against C. elegans and against H. contortus in the jird. Purified and/or synthetic samples of dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 were tested in the jird model; only dioxapyrrolomycin exhibited appreciable activity against H. contortus (greater than or equal to 90.9% clearance at 0.33 mg/jird), while none of the compounds showed appreciable activity against T. colubriformis. Dioxapyrrolomycin cleared 99.9% of H. contortus from lambs at 12.5 mg/kg. An in vitro migration study using susceptible and closantel-resistant H. contortus showed there is cross-resistance between dioxapyrrolomycin and closantel. Dioxapyrrolomycin appears to be a narrow-spectrum anthelmintic which works through a closantel-like mode-of-action.
authors.affiliation: Upjohn Laboratories, Parasitology Research and Chemical and Biological Screening, Kalamazoo, Michigan 49001.
authors.forename: G A
authors.initials: GA
authors.lastname: Conder
authors.forename: R J
authors.initials: RJ
authors.lastname: Zielinski
authors.forename: S S
authors.initials: SS
authors.lastname: Johnson
authors.forename: M S
authors.initials: MS
authors.lastname: Kuo
authors.forename: D L
authors.initials: DL
authors.lastname: Cox
authors.forename: V P
authors.initials: VP
authors.lastname: Marshall
authors.forename: C L
authors.initials: CL
authors.lastname: Haber
authors.forename: P J
authors.initials: PJ
authors.lastname: DiRoma
authors.forename: S J
authors.initials: SJ
authors.lastname: Nelson
authors.forename: R D
authors.initials: RD
authors.lastname: Conklin
mesh_terms: D000192:Actinomycetales / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000302:isolation & purification / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D011758:Pyrroles / Q000302:isolation & purification / Q000494:pharmacology; D012756:Sheep
chemical_list: D000871:Anthelmintics; D000900:Anti-Bacterial Agents; D011758:Pyrroles; C053531:pyrroxamycin