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.
Perry
M Jesus
MJ
iMedUL, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal.
Mendes
Eduarda
E
Simplício
Ana Luísa
AL
Coelho
Ana
A
Soares
Ricardo V
RV
Iley
Jim
J
Moreira
Rui
R
Francisco
Ana Paula
AP
D000363:Agaricales / Q000201:enzymology; D000478:Alkylation; D004298:Dopamine / Q000031:analogs & derivatives*; D015195:Drug Design; D004355:Drug Stability; D004789:Enzyme Activation; D006801:Humans; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D014226:Triazenes / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D014439:Tyramine / Q000031:analogs & derivatives*
D011355:Prodrugs; D014226:Triazenes; D014442:Monophenol Monooxygenase; D004298:Dopamine; D014439:Tyramine