Kinetics of hydrolysis of acetyl, valeroyl and nicotinoyl acyl derivatives of stobadine.
The present work deals with the kinetics of hydrolysis of the acyl derivatives of stobadine, an originally synthesized potential antiarrhythmic and antihypoxic drug, which was found to have also an excellent scavenging effect on reactive oxygen species. The acyl derivatives of stobadine, which possess high lipophilicity, represent model blood-brain barrier penetrating agents. It is assumed that the acyl derivatives of stobadine may act as prodrugs which are hydrolysed in different biological tissues to release the active drug. The decomposition of three acyl derivatives of stobadine was studied in acidic, basic and neutral buffer solutions at constant ionic strength (0.1 mol/L) at 25 degrees and 70 degrees C using UV spectrophotometric method. The pseudo first-order rate constants and the pH-rate profile for the degradation of acetyl-, valeroyl- and nicotinoyl-derivatives of stobadine were determined. Confirmation that stobadine was the first degradation product was provided by thin-layer chromatography.
Stankovicová
M
M
Department of Pharmaceutical Chemistry, Faculty of Pharmacy of Comenius University, Bratislava, Slovak Republic.
Bezáková
Z
Z
Benes
L
L
D000085:Acetates / Q000737:chemistry; D000889:Anti-Arrhythmia Agents / Q000737:chemistry*; D000975:Antioxidants / Q000737:chemistry*; D002021:Buffers; D002243:Carbolines / Q000737:chemistry*; D002855:Chromatography, Thin Layer; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009539:Nicotinic Acids / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D014631:Valerates / Q000737:chemistry
D000085:Acetates; D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D002021:Buffers; D002243:Carbolines; D009539:Nicotinic Acids; D011355:Prodrugs; D014631:Valerates; C100106:dicarbine