NEW GALACTOSYLATED NSAIDs PRODRUGS IN A GREEN CONTEXT: SYNTHESIS AND STABILITYAbstract
Prodrug approach is a new frontier that reinforces the concept of green chemistry in the pharmaceutical chemistry field. The combination of a suitable synthesis and the strategy of the prodrug is of huge advantage for pharmaceutical industries. In this paper, we compare the conventional synthesis of new galactosylated NSAIDs prodrugs with green strategies and demonstrate how we can move away from the use of harmful substances using a suitable method for the synthesis of new compounds. So, we decided to investigate the use of potentially cleaner solvents and reagents such as room temperature ionic liquids, hydrochloric acid and glacial acetic acid. Furthermore, the chemical and enzymatic stabilities of new NSAIDs prodrugs were evaluated in order to determine both their stability in an aqueous solution at pH=1 and pH=7.4 and their feasibility in undergoing enzymatic cleavage by plasma to regenerate the original drug. Results concerning green synthetic approach clearly showed a reduction of time and waste. Moreover, these prodrugs are susceptible to degradation in rat plasma but stable to chemical hydrolysis.
S. Magliocca *, F. Sodano, M. Nieddu, L. Burrai, G. Boatto and M. Grazia Rimoli
Department of Pharmacy 1, “Federico II” University of Naples, Naples, Italy
15 September, 2016
14 November, 2016
25 November, 2016
01 April, 2017