title: Novel triclabendazole prodrug: A highly water soluble alternative for the treatment of fasciolosis.
abstract: In this work we present the synthesis, aqueous solubility and stability, hydrolysis by alkaline phosphatase, and in vivo fasciolicidal activity in sheep of a highly water soluble phosphate salt prodrug of triclabendazole (MFR-5). The aqueous solubility of MFR-5 at pH 7 was 88,000-fold that of triclabendazole. MFR-5 showed excellent aqueous stability (>95% after 26h) at pH 7, making it ideal for developing pharmaceutical compositions in the form of solutions that can easily be hydrolyzed by the enzyme alkaline phosphatase (t=13.6s) to liberate the precursor compound. An aqueous solution of MFR-5 administered intramuscularly to sheep at concentrations of 4, 6 and 8mg/kg presented a fasciolicidal efficiency of 96.5%, 98.4% and 99.2%, respectively. In the in vivo experiments, MFR-5 reduced 100% the excretion of eggs in all of the above concentrations.
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Av. Universidad 3000, CDMX, México 04510, Mexico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Flores-Ramos
authors.affiliation: Facultad de Medicina Veterinaria y Zootecnia, Departamento de Parasitología, Universidad Nacional Autónoma de México, Av. Universidad 3000, CDMX, México 04510, Mexico.
authors.forename: Froylán
authors.initials: F
authors.lastname: Ibarra-Velarde
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Av. Universidad 3000, CDMX, México 04510, Mexico.
authors.forename: Helgi
authors.initials: H
authors.lastname: Jung-Cook
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Av. Universidad 3000, CDMX, México 04510, Mexico.
authors.forename: Alicia
authors.initials: A
authors.lastname: Hernández-Campos
authors.affiliation: Facultad de Medicina Veterinaria y Zootecnia, Departamento de Parasitología, Universidad Nacional Autónoma de México, Av. Universidad 3000, CDMX, México 04510, Mexico.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Vera-Montenegro
authors.affiliation: Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Av. Universidad 3000, CDMX, México 04510, Mexico. Electronic address: rafaelc@unam.mx.
authors.forename: Rafael
authors.initials: R
authors.lastname: Castillo
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D005210:Fasciola hepatica / Q000187:drug effects / Q000254:growth & development; D005211:Fascioliasis / Q000188:drug therapy; D010755:Organophosphates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010063:Ovum / Q000187:drug effects; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D012756:Sheep; D012995:Solubility; D000077682:Triclabendazole; D014867:Water / Q000737:chemistry*
chemical_list: D001562:Benzimidazoles; C000621041:MFR-5a compound; C000621042:MFR-5b compound; D010755:Organophosphates; D011355:Prodrugs; D014867:Water; D000077682:Triclabendazole
keywords: Benzimidazole; Fasciola hepatica; Fasciolicidal activity; Phosphonooxymethyl; Prodrug; Triclabendazole