Synthesis of Nitric Oxide Donors Derived from Piloty’s Acid and Study of Their Effects on Dopamine Secretion from PC12 Cells

This study investigated the mechanisms and kinetics of nitric oxide (NO) generation by
derivatives of Piloty’s acid (NO-donors) under physiological conditions. In order to qualitatively
and quantitatively measure NO release, electron paramagnetic resonance (EPR) was carried out
with NO spin trapping. In addition, voltammetric techniques, including cyclic voltammetry
and constant potential amperometry, were used to confirm NO release from Piloty’s acid and its
derivatives. The resulting data showed that Piloty’s acid derivatives are able to release NO under
physiological conditions. In particular, electron-withdrawing substituents favoured NO generation,
while electron-donor groups reduced NO generation. In vitro microdialysis, performed on PC12
cell cultures, was used to evaluate the dynamical secretion of dopamine induced by the Piloty’s
acid derivatives. Although all the studied molecules were able to induce DA secretion from PC12,
only those with a slow release of NO have not determined an autoxidation of DA itself. These results
confirm that the time-course of NO-donors decomposition and the amount of NO released play a
key role in dopamine secretion and auto-oxidation. This information could drive the synthesis or the
selection of compounds to use as potential drugs for the therapy of Parkinson’s disease (PD).