Synthesis of cysteinylphenol, cysteaminylphenol, and related compounds, and in vivo evaluation of antimelanoma effect.
Phenolic and catecholic compounds were synthesized, by combination with cysteine or cysteamine through thioether bond, and their antimelanoma and melanocytotoxic effects were evaluated. Among nine compounds tested, 4-S-cysteaminylphenol (CAP) resulted in an increase in the life span (% ILS) of melanoma-bearing mice and in the growth inhibition (% GI) of melanoma tissue. 4-S-Cysteinylphenol (CP) and its methyl ester form also showed some increase in % GI. The 2-S-isomers of CP and CAP and diphenolic derivatives of CP did not show any significant antimelanoma effect. In addition, the s.c. injection of 4-S-CAP and 4-S-CP, in particular 4-S-CAP, caused the depigmentation of black hair which was manifested by loss of functioning melanocytes, as seen under light microscopy. The 4-S-CAP appears to provide a basis for development of a new class of antimelanoma and melanocytotoxic agents that are more stable than catecholic compounds, which have been most widely utilized as a source of rational chemotherapy for malignant melanoma.
Miura
S
S
Department of Dermatology, Sapporo Medical College, Japan.
Ueda
T
T
Jimbow
K
K
Ito
S
S
Fujita
K
K
D000818:Animals; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006200:Hair Color / Q000187:drug effects; D008544:Melanocytes / Q000187:drug effects; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012878:Skin Neoplasms / Q000188:drug therapy*
D003543:Cysteamine; C043036:4-S-cysteinylphenol; C043037:4-S-cysteaminylphenol; D003545:Cysteine