Comparison of in vivo anti-melanoma effect of enantiomeric alpha-methyl- and alpha-ethyl-4-S-cysteaminylphenol.

Abstract

Melanogenesis appears to be a unique target to develop anti-tumour agents specific for malignant melanoma. Among the anti-melanoma compounds that we have examined, 4-S-cysteaminylphenol (4-S-CAP), a phenolic amine, was found to have the most promising anti-melanoma effects. To further improve the efficacy as anti-melanoma agents, we have recently synthesized enantiomers of alpha-Me-4-S-CAP and alpha-Et-4-S-CAP. The enantiomers were found to be good substrates for tyrosinase. In vitro experiments showed that the enantiomers were highly cytotoxic to B16-F1 melanoma cells, and the cytotoxic effect was proved to be tyrosinase-dependent. In the present study, in vivo cytotoxicity experiments showed that i.p. administration of R-alpha-Me-4-S-CAP and S-alpha-Et-4-S-CAP (and 4-S-CAP) strongly inhibited the subcutaneous growth of B16 melanoma in mice, while the corresponding enantiomers were much less effective. Similarly, i.p. treatment with R-alpha-Me-4-S-CAP or S-alpha-Et-4-S-CAP, but not with 4-S-CAP, caused strong depigmentation of follicular melanocytes in C57BL black mice. Among 4-S-CAP and the enantiomers, only R-alpha-Et-4-S-CAP caused a moderate decrease in blood pressure in spontaneously hypertensive rats. These results confirm that the use of enantiomers increases the efficacy of tyrosinase-dependent cytotoxic phenolic amines.

• Authors: Jun Yukitake, Hiromi Otake, Shigeki Inoue, Kazumasa Wakamatsu, Shosuke Ito
• Journal: Melanoma research (Melanoma Res) Vol. 14 Issue 2 Pg. 115-20 (Apr 2004) ISSN: 0960-8931 [Print] England
• PMID: 15057040 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Antineoplastic Agents
• ethyl-4-S-cysteaminylphenol
• methyl-4-S-cysteaminylphenol
• Cysteamine

Topics

• Animals
• Antihypertensive Agents (administration & dosage, pharmacology, therapeutic use)
• Antineoplastic Agents (administration & dosage, pharmacology, therapeutic use)
• Cell Proliferation (drug effects)
• Cysteamine (administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
• Hypotension (blood)
• Melanoma, Experimental (drug therapy)
• Mice
• Mice, Inbred C57BL
• Pigmentation (drug effects)
• Rats
• Rats, Inbred SHR
• Skin Neoplasms (drug therapy)
• Stereoisomerism
• Xenograft Model Antitumor Assays