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.