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

被引：29
作者：
Knaggs, S
Malkin, H
Osborn, HMI [1 ]
Williams, NAO
Yaqoob, P
机构：
[1] Univ Reading, Sch Pharm, Reading RG6 6AD, Berks, England
[2] Univ Reading, Sch Chem, Reading RG6 6AD, Berks, England
[3] Univ Reading, Sch Food Biosci, Reading RG6 6AP, Berks, England
来源：
ORGANIC & BIOMOLECULAR CHEMISTRY | 2005年 / 3卷 / 21期
关键词：
D O I：
10.1039/b506404j
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
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.
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页码：4002 / 4010
页数：9
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