1. New prodrugs derived from 6-aminodopamine and 4-aminophenol as candidates for melanocyte-directed enzyme prodrug therapy (MDEPT)
- Author
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Hugh Malkin, Helen M. I. Osborn, Nana Aba Williams, Sarah Knaggs, and Parveen Yaqoob
- Subjects
Cell Survival ,Dopamine ,Tyrosinase ,Melanocyte ,Aminophenols ,Biochemistry ,chemistry.chemical_compound ,Drug Delivery Systems ,Cell Line, Tumor ,medicine ,Humans ,Urea ,Prodrugs ,Physical and Theoretical Chemistry ,Bovine serum albumin ,Cytotoxicity ,Melanoma ,chemistry.chemical_classification ,biology ,Monophenol Monooxygenase ,Organic Chemistry ,Prodrug ,Enzyme ,medicine.anatomical_structure ,chemistry ,Thiourea ,Drug delivery ,biology.protein ,Melanocytes ,Drug Screening Assays, Antitumor - 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.
- Published
- 2005