Synthesis and pharmaceutical properties of N-acyloxymethyl prodrugs of Allop with potential anti-trypanosomal activity

GUALDESI, MARÍA S.; ORTIZ, CRISTINA S.; RAVIOLO, MÓNICA A

DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY

TAYLOR & FRANCIS INC

Lugar: Londres; Año: 2016 vol. 42 p. 606 - 610

0363-9045

We report herein the synthesis, and the physicochemical and pharmacokinetic properties ofN-acyloxymethyl prodrugs of allopurinol (Allop) (2a?f). Allop is a compound with activityagainst Trypanosoma cruzi, a causative agent of Chagas disease. Its pathology leads to a hugenumber of infections and deaths per year, because in addition to many sufferers only havinglimited access to health services only an inefficient chemotherapy is available. Relevantpharmaceutical properties (pKa, stability, solubility, lipophilicity, in vitro permeability, bindingprotein, xanthine oxidase binding) were also determined. The results obtained showed thatderivatives behave as prodrugs of Allop, since they exhibit improved physicochemical andpharmacokinetic properties relative to their precursor. This behavior turns these compoundsinto active reservoirs of Allop, and reduces its unfavorable characteristics, so 2a?f compoundsare excellent candidates for the treatment of Chagas disease. This work is therefore animportant contribution leading to the suppression of Chagas disease.