New prodrugs derived from 6-aminodopamine and 4-aminophenol as candidates for melanocyte-directed enzyme prodrug therapy (MDEPT)

Research output: Contribution to journalArticle

Authors

  • Sarah Knaggs
  • Hugh Malkin
  • Helen M I Osborn
  • Nana Aba O Williams
  • Parveen Yaqoob

Colleges, School and Institutes

Abstract

Two novel tyrosinase mediated drug delivery pathways have been investigated for the selective delivery of cytotoxic units to melanocytes from urea and thiourea prodrugs. The synthesis of these prodrugs is reported, as well as oximetry data that illustrate that the targets are substrates for tyrosinase. The stability of each of the prodrugs in (i) phosphate buffer and (ii) bovine serum is discussed, and the urea prodrugs are identified as lead candidates for further studies. Finally, HPLC studies and preliminary cytotoxicity studies in a melanotic and an amelanotic cell line, that illustrate the feasibility of the approach, are presented.

Details

Original languageEnglish
Pages (from-to)4002-10
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume3
Issue number21
Publication statusPublished - 2005