title: Dopamine- and tyramine-based derivatives of triazenes: activation by tyrosinase and implications for prodrug design.
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.
authors.affiliation: iMedUL, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: M Jesus
authors.initials: MJ
authors.lastname: Perry
authors.forename: Eduarda
authors.initials: E
authors.lastname: Mendes
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Simplício
authors.forename: Ana
authors.initials: A
authors.lastname: Coelho
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Soares
authors.forename: Jim
authors.initials: J
authors.lastname: Iley
authors.forename: Rui
authors.initials: R
authors.lastname: Moreira
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Francisco
mesh_terms: 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*
chemical_list: D011355:Prodrugs; D014226:Triazenes; D014442:Monophenol Monooxygenase; D004298:Dopamine; D014439:Tyramine