Dissociation and electrooxidation of primaquine diphosphate as an approach to the study of anti-chagas prodrugs mechanism of action.
This paper describes the voltammetric behavior of primaquine as a previous support to the further understanding of the delivery and action mechanisms of its respective synthesized prodrugs. There are few papers describing the drug behavior and most of the time no correlation between oxidation process and pH is done. Our results showed that primaquine oxidation is a one-step reaction involving two electrons with the charge transfer process being strongly pH-dependent in acid medium and pH-independent in a weak basic medium, with the neutral form being easily oxidized. This leads to the conclusion that quinoline nitrogen ring neutralization is a determinant step to the formation of the oxidized primaquine form. The existence of a relationship between the primaquine dissociation equilibrium and its electrooxidation process is shown. This work points the importance of voltammetric methodology as a tool for further studies on quantitative relationship studies between chemical structure and biological activity (QSAR) for electroactive drugs.
La-Scalea
M A
MA
Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, USP, São Paulo, Brazil. scalea@usp.br
Chin
C M
CM
Cruz
M L
ML
Serrano
S H
SH
Ferreira
E I
EI
D000981:Antiprotozoal Agents / Q000737:chemistry*; D014355:Chagas Disease / Q000188:drug therapy; D004563:Electrochemistry; D004566:Electrodes; D004579:Electron Transport; D006863:Hydrogen-Ion Concentration; D010084:Oxidation-Reduction; D011319:Primaquine / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*
D000981:Antiprotozoal Agents; D011355:Prodrugs; D011319:Primaquine