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The in vivo antimelanoma effect of 4‐S‐cysteaminylphenol and its N‐acetyl derivative
Author(s) -
Miura Takako,
Jimbow Kowichi,
Ito Shosuke
Publication year - 1990
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910460530
Subject(s) - in vivo , melanoma , melanin , tyrosinase , chemistry , in vitro , biochemistry , pharmacology , stereochemistry , enzyme , cancer research , biology , microbiology and biotechnology
Phenolic melanin precursors can be utilized for the development of anti‐melanoma agents. The sulphur homologue of tyrosine, 4‐S‐cysteinylphenol (CP) and its decarboxylation product, 4‐S‐cysteaminylphenol (CAP) were shown to be substrates of melanoma tyrosinase, forming melanin‐like pigment. Both, but in particular the 4‐S‐CAP, exhibited a significant in vivo depigmenting effect. Here, we report on the in vivo anti‐melanoma effect of 4‐S‐CP, and 4‐S‐CAP and its N‐acetyl derivative. In a previous in vitro study, it was shown that 4‐S‐CP and 4‐S‐CAP required a catalytic amount of dopa for optimal mammalian tyrosinase activity. To enhance the potential anti‐melanoma effect of these two compounds, L‐dopa and a decarboxylase inhibitor (carbidopa) were given concomitantly. We found that 4‐S‐CAP showed a significant growth inhibition of B16 melanoma inoculated S. C. into C57BL/6J mice. The anti‐melanoma effect was increased significantly by combination of L‐dopa and carbidopa. In addition, we tested the in vivo anti‐melanoma effect of an N‐acetyl derivative of 4‐S‐CAP (N‐Ac‐4‐S‐CAP). We found that N‐Ac‐4‐S‐CAP was the tyrosinase substrate and potent inhibitor of melanoma growth. N‐acetyl 4‐S‐CAP showed a marked increase in water solubility. We suggest that N‐Ac‐4‐S‐CAP may prove to be a valuable model for the development of anti‐melanoma agent using a metabolic pathway of melanin synthesis.