M. Stankovicova et al., Kinetics of hydrolysis of acetyl, valeroyl and nicotinoyl acyl derivativesof stobadine, LIFE SCI, 65(18-19), 1999, pp. 2007-2010
The present work deals with the kinetics of hydrolysis of the acyl derivati
ves of stobadine, an originally synthesized potential antiarrhythmic and an
tihypoxic drug, which was found to have also an excellent scavenging effect
on reactive oxygen species. The acyl derivatives of stobadine, which posse
ss high lipophilicity, represent model blood-brain barrier penetrating agen
ts. It is assumed that the acyl derivatives of stobadine may act as prodrug
s which are hydrolysed in different biological tissues to release the activ
e drug. The decomposition of three acyl derivatives of stobadine was studie
d in acidic, basic and neutral buffer solutions at constant ionic strength
(0.1mol/L) at 25 degrees and 70 degrees C using UV spectrophotometric metho
d. The pseudo first-order rate constants and the pH-rate profile for the de
gradation of acetyl-, valeroyl- and nicotinoyl-derivatives of stobadine wer
e determined. Confirmation that stobadine was the first degradation product
was provided by thin-layer chromatography.