Schiff bases derived from p-aminobenzyl alcohol as trigger groups for pH-dependent prodrug activation

A number of novel acid-sensitive Schiff bases derived from p-aminobenzyl alcohol and various benzaldehyde derivatives were synthesized and were subsequently shown to trigger benzyl elimination reactions. The kinetics of acid-catalyzed hydrolysis at pH 5.0 as well as stability at pH 7.4 were studied using fluorogenic model compounds. Two fluoro-substituted Schiff bases showed efficient hydrolysis at pH 5.0 combined with a long-term stability at pH 7.4 and are considered suitable candidates for the development of anticancer prodrugs.