title: A highly water soluble benzimidazole derivative useful for the treatment of fasciolosis.
abstract: This study describes the synthesis of compound (7), a highly hydrosoluble phosphonooxymethyl prodrug of compound alpha (4). Compound (7) improved the aqueous solubility of its precursor compound (4) by 50,000 times and it is stable at neutral pH. The prodrug showed faciolicidal activity when evaluated in vitro against excysted Fasciola hepatica metacercariae. The in vivo evaluation of (7) was carried out via oral, intramuscular and subcutaneous administration in sheep artificially infected with F. hepatica metacercariae. At an intramuscular dose of 4 mg/kg, the activity of (7) was similar to that of compound alpha (4) at an oral dose of 15 mg/kg.
authors.affiliation: Facultad de Química, Departamento de Farmacia, UNAM, México DF 04510, Mexico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Flores-Ramos
authors.affiliation: Facultad de Medicina Veterinaria y Zootecnia, Departamento de Parasitología, UNAM, México, DF 04510, Mexico.
authors.forename: Froylán
authors.initials: F
authors.lastname: Ibarra-Velarde
authors.affiliation: Facultad de Química, Departamento de Farmacia, UNAM, México DF 04510, Mexico.
authors.forename: Alicia
authors.initials: A
authors.lastname: Hernández-Campos
authors.affiliation: Facultad de Medicina Veterinaria y Zootecnia, Departamento de Parasitología, UNAM, México, DF 04510, Mexico.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Vera-Montenegro
authors.affiliation: Facultad de Química, Departamento de Farmacia, UNAM, México DF 04510, Mexico.
authors.forename: Helgi
authors.initials: H
authors.lastname: Jung-Cook
authors.affiliation: Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Qro. CP. 76230, Mexico.
authors.forename: Germinal J
authors.initials: GJ
authors.lastname: Cantó-Alarcón
authors.affiliation: Facultad de Química, Departamento de Farmacia, UNAM, México DF 04510, Mexico.
authors.forename: Lauro Misael
authors.initials: LM
authors.lastname: Del Rivero
authors.affiliation: Facultad de Química, Departamento de Farmacia, UNAM, México DF 04510, Mexico. Electronic address: rafaelc@unam.mx.
authors.forename: Rafael
authors.initials: R
authors.lastname: Castillo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D005210:Fasciola hepatica / Q000187:drug effects; D005211:Fascioliasis / Q000188:drug therapy* / Q000469:parasitology / Q000662:veterinary; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D010755:Organophosphates / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012756:Sheep; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000981:Antiprotozoal Agents; D001562:Benzimidazoles; D010755:Organophosphates; D011355:Prodrugs; D014867:Water; C031000:benzimidazole
keywords: Benzimidazole; Compound alpha; Fasciola hepatica; Fasciolicidal activity; Phosphonooxymethyl; Prodrug