title: Synthesis and pharmaceutical properties of N-acyloxymethyl prodrugs of Allop with potential anti-trypanosomal activity.
abstract: We report herein the synthesis, and the physicochemical and pharmacokinetic properties of N-acyloxymethyl prodrugs of allopurinol (Allop) (2a-f). Allop is a compound with activity against Trypanosoma cruzi, a causative agent of Chagas disease. Its pathology leads to a huge number of infections and deaths per year, because in addition to many sufferers only having limited access to health services only an inefficient chemotherapy is available. Relevant pharmaceutical properties (pKa, stability, solubility, lipophilicity, in vitro permeability, binding protein, xanthine oxidase binding) were also determined. The results obtained showed that derivatives behave as prodrugs of Allop, since they exhibit improved physicochemical and pharmacokinetic properties relative to their precursor. This behavior turns these compounds into active reservoirs of Allop, and reduces its unfavorable characteristics, so 2a-f compounds are excellent candidates for the treatment of Chagas disease. This work is therefore an important contribution leading to the suppression of Chagas disease.
authors.affiliation: a Departamento de Farmacia, Facultad de Ciencias Químicas , Universidad Nacional de Córdoba , Córdoba , Argentina.
authors.forename: M S
authors.initials: MS
authors.lastname: Gualdesi
authors.affiliation: a Departamento de Farmacia, Facultad de Ciencias Químicas , Universidad Nacional de Córdoba , Córdoba , Argentina.
authors.forename: C S
authors.initials: CS
authors.lastname: Ortiz
authors.affiliation: a Departamento de Farmacia, Facultad de Ciencias Químicas , Universidad Nacional de Córdoba , Córdoba , Argentina.
authors.forename: M A
authors.initials: MA
authors.lastname: Raviolo
mesh_terms: D000493:Allopurinol / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D006801:Humans; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000502:physiology
chemical_list: D011355:Prodrugs; D014344:Trypanocidal Agents; D000493:Allopurinol
keywords: Chagas disease; N-acyloxymethyl prodrugs; Trypanosoma cruzi; physicochemical and pharmacokinetic properties; trypanosomal activity