title: Antischistosomal versus antiandrogenic properties of aryl hydantoin Ro 13-3978.
abstract: In the early 1980s, the antischistosomal aryl hydantoin Ro 13-3978 (AH01), a close structural analogue of the androgen receptor antagonist nilutamide, was discovered. Administration of 100 mg/kg oral doses of AH01 to mice infected with adult and juvenile Schistosoma mansoni produced 95% and 64% total worm burden reductions, confirming its high activity against adult worms, and showing that AH01 is also effective against juvenile infections. AH01 had no measureable interaction with the androgen receptor in a ligand competition assay, but it did block dihydrotestosterone-induced cell proliferation in an androgen-dependent human prostate cancer cell line. For AH01, nilutamide, and three closely related aryl hydantoin derivatives, there was no correlation between antischistosomal activity and androgen receptor interaction.
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Chunkai
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Jaeki
authors.initials: J
authors.lastname: Min
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Sakthivel
authors.initials: S
authors.lastname: Muniyan
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Mireille
authors.initials: M
authors.lastname: Vargas
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Dong
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: R Kiplin
authors.initials: RK
authors.lastname: Guy
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Lin
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keiser
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland jvenners@unmc.edu.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Vennerstrom
mesh_terms: D059002:Androgen Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D006827:Hydantoins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D048289:Imidazolidines / Q000494:pharmacology; D008297:Male; D051379:Mice; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000254:growth & development; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000469:parasitology; D012556:Schistosomicides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D059002:Androgen Receptor Antagonists; D006827:Hydantoins; D048289:Imidazolidines; C000591057:Ro 13-3978; D012556:Schistosomicides; D013196:Dihydrotestosterone; C021277:nilutamide