Dopamine- and tyramine-based derivatives of triazenes

Abstract

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. (C) 2009 Elsevier Masson SAS. All rights reserved.. - Fundacao para a Ciencia e Tecnologia (Portugal). - The authors thank the Fundacao para a Ciencia e Tecnologia (Portugal) for financial support through their pluriannual funding to the iMed.UL research unit.