Dopamine- and tyramine-based derivatives of triazenes: Activation by tyrosinase and implications for prodrug design

A range of triazene derivatives were synthesized and investigated as prodrug candidates for melanocyte-directed enzyme prodrug therapy (MDEPT). The prodrugs contained a tyramine or dopamine promoiety required for tyrosinase activation and this was joined via a urea functional group to the cytotoxic triazene. The stability of each of the prodrugs in phosphate buffer, human plasma and in mushroom tyrosinase is discussed. The identification of the main peak formed after the tyrosinase reaction was attempted by LC–MS and the conversion of prodrug to the quinone was confirmed.

Graphical abstract We report the synthesis of triazene derivatives and their evaluation as substrates for tyrosinase. The conversion of prodrugs to the ortho-quinone was confirmed by LC–MS.Figure optionsDownload full-size imageDownload as PowerPoint slide