Kinetics of hydrolysis of acetyl, valeroyl and nicotinoyl acyl derivativesof stobadine

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.