Development of novel derivatives for allopurinol in the treatment of Chagas’ disease — ASN Events
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  3. Development of novel derivatives for allopurinol in the treatment of Chagas’ disease

Development of novel derivatives for allopurinol in the treatment of Chagas’ disease (#230)

Josep Esteve-Romero 1 , Monica-Ana Raviolo 2 , Margarita Briñon 2 , Christian Muñoz-Sosa 2 , Juan Péris-Vicente 1 , Samuel Carda-Broch 1 , Enrique Ochoa-Aranda 3
  1. Química Bioanalítica - QFA - ESTCE, Universitat Jaume I, Castelló, La Plana, Spain
  2. Departamento de Farmacia, Universidad Nacional de Córdoba, Córdoba, Argentina
  3. Biopatologia Molecular, Hospital Provincial, Castelló de la Plana, Spain

The aim of the current study was to establish inherent stability of derivatives of allopurinol (Allop), as potential antitrypanosomal drugs (etiologic agent of Chagas' disease), using an HPLC method. FDA guideline was used to validated the new method, purposed for four novel derivatives of Allop, including the percentages of degradation of each derivative, in simulated gastric fluid (SGF) and pH 1.2 (1 h of incubation, 37ºC); simulated intestinal fluid (SIF) and pH 6.8 (3 h of incubation, 37ºC); as oxidizing agent H2O2 (30%, 25ºC,); and hydrolytic studies with HCl, NaOH and H2O (0.1 M, 90ºC, 12h.
All derivatives were stable in pH 1.2, SGF and pH 6.8. In SIF, derivatives show instability is related to the increase in the lipophilicity of the compound. In NaOH, all derivatives suffer immediate degradation, in H2O only degrades more lipophilic compound, and in HCl and H2O2, the compounds are degraded without maintaining a connection with some measured property. All derivatives show degradationunder a pseudo-first-order kinetics.

 

Acknowledgments: This work was supported by Projects Res. Nº 162/12 of Secretaria de Ciencia y Técnica – UNC and P1.1B2012-36 of Pla de Promoció de la Investigació de la Universitat Jaume I.