Abstract：
:A phenolic amine compound, 4-S-cysteaminylphenol (4-S-CAP), is a potent depigmenting agent. To develop more efficacious antimelanoma agents, we synthesized four homologues of 4-S-CAP: N-acetyl-4-S-CAP (N-Ac-4-S-CAP), alpha-methyl-4-S-CAP, 4-S-homo-CAP, and N,N'-dimethyl-4-S-CAP. We tested these five compounds in mice in vivo. After s.c. or i.p. injection of saline solution (in control groups) or one of the compounds, follicular melanocytes were examined by light and electron microscopy to assess the degree of melanocytotoxicity; N-Ac-4-S-CAP induced the most depigmentation (98%), whether given i.p. or s.c. After injection of 4-S-CAP or N-Ac-4-S-CAP, the number of murine B16F10 melanoma colonies formed in the lungs was determined; 4-S-CAP and N-Ac-4-S-CAP were almost equally effective, reducing the colonies to 32 and 25% of mean control, respectively. Metabolic studies of the urine showed 9% of 4-S-CAP and 20% of N-Ac-4-S-CAP injected i.p. were excreted unchanged in 24 h; 1.3% of the N-Ac-4-S-CAP was excreted as 4-S-CAP, indicating some conversion. We conclude that N-Ac-4-S-CAP is a suitable model for developing chemotherapy to treat melanoma characterized by high tyrosinase activity and melanin synthesis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Alena F,Jimbow K,Ito Ssubject
Has Abstractpub_date
1990-06-15 00:00:00pages
3743-7issue
12eissn
0008-5472issn
1538-7445journal_volume
50pub_type
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