Hydrolysis kinetics and photolysis kinetics of N1-retinoyl-5-fluorouracil

The kinetics of hydrolysis and photolysis of N 1 -retinoyl-5-fluorouracil (designated Re-5-Fu) in buffer solution and in biological media were studied to assess its feasibility as a prodrug for 5-fluorouracil (designated 5-Fu). The mechanism of the hydrolysis is also discussed. Hydrolysis of Re-5-Fu yields 5-Fu in quantitative amounts. The pH-rate profile obtained revealed the occurrence of acid and base catalysed as well as a spontaneous or water-catalysed hydrolysis. The rates of hydrolysis were remarkably accelerated in the presence of biological media. The study of photolysis kinetics showed that Re-5-Fu is a photosensitive compound. The Re-5-Fu is more lipophilic than 5-Fu as shown by the partition coefficient in a 1-octanol-aqueous buffer system.