Miura T, Jimbow K, Ito S
Department of Dermatology, Sapporo Medical College, Japan.
Int J Cancer. 1990 Nov 15;46(5):931-4. doi: 10.1002/ijc.2910460530.
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.
酚类黑色素前体可用于开发抗黑色素瘤药物。酪氨酸的硫类似物4 - S - 半胱氨酰苯酚（CP）及其脱羧产物4 - S - 半胱胺基苯酚（CAP）被证明是黑色素瘤酪氨酸酶的底物，可形成类黑色素。二者，尤其是4 - S - CAP，在体内表现出显著的色素脱失作用。在此，我们报告4 - S - CP、4 - S - CAP及其N - 乙酰衍生物的体内抗黑色素瘤作用。在之前的一项体外研究中，结果表明4 - S - CP和4 - S - CAP需要催化量的多巴才能实现最佳的哺乳动物酪氨酸酶活性。为增强这两种化合物潜在的抗黑色素瘤作用，同时给予左旋多巴和一种脱羧酶抑制剂（卡比多巴）。我们发现4 - S - CAP对皮下接种到C57BL / 6J小鼠体内的B16黑色素瘤具有显著的生长抑制作用。左旋多巴和卡比多巴联合使用可显著增强抗黑色素瘤作用。此外，我们测试了4 - S - CAP的N - 乙酰衍生物（N - Ac - 4 - S - CAP）的体内抗黑色素瘤作用。我们发现N - Ac - 4 - S - CAP是酪氨酸酶底物且是黑色素瘤生长的有效抑制剂。N - 乙酰4 - S - CAP的水溶性显著增加。我们认为，N - Ac - 4 - S - CAP可能被证明是利用黑色素合成代谢途径开发抗黑色素瘤药物的有价值模型。
