Melanocytotoxicity and antimelanoma effects of phenolic amine compounds in mice in vivo

• Published in: Cancer research (Chicago, Ill.) Vol. 50; no. 12; pp. 3743 - 3747
• Main Authors: ALENA, F, JIMBOW, K, ITO, S
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.06.1990
• Subjects: 550600 > Medicine; ANIMAL CELLS; ANIMALS; Antineoplastic agents; ANTINEOPLASTIC DRUGS; AROMATICS; Biological and medical sciences; BIOLOGICAL EFFECTS; CHEMICAL PREPARATION; CHEMOTHERAPY; COLONY FORMATION; Cysteamine - administration & dosage; Cysteamine - pharmacology; DISEASES; DRUGS; EXPERIMENTAL NEOPLASMS; Female; Hair - analysis; Hair Color - drug effects; HYDROXY COMPOUNDS; IN VIVO; INHIBITION; INJECTION; Injections, Intraperitoneal; Injections, Subcutaneous; INTAKE; INTRAPERITONEAL INJECTION; MAMMALS; Medical sciences; MELANIN; Melanins - analysis; Melanocytes - drug effects; Melanocytes - ultrastructure; Melanoma, Experimental - drug therapy; MELANOMAS; MICE; Mice, Inbred C57BL; NEOPLASMS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; Pharmacology. Drug treatments; PHENOLS; Phenols - administration & dosage; Phenols - pharmacology; Pigmentation - drug effects; PIGMENTS; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; RADIOLOGY AND NUCLEAR MEDICINE; RODENTS; SUBCUTANEOUS INJECTION; SYNTHESIS; THERAPY; TUMOR CELLS; VERTEBRATES 560300 > Chemicals Metabolism & Toxicology; Therapeutic efficiency; Hypomelanosis; Rodentia; Electron microscopy; Organic sulfide; Pathology; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Amine; Structure activity relation; Mouse; Animal; B16-Melanoma; Malignant melanoma; Aromatic compound; Melanin
• ISSN: 0008-5472; 1538-7445

A phenolic amine compound, 4-S-cysteaminylphenol (4-S-CAP), is a potent depigmenting agent. To develop more efficacious antimelanoma agents, we synthesized four homologues of 4-S-CAP: N-acetyl-4-S-CAP (N-Ac-4-S-CAP), alpha-methyl-4-S-CAP, 4-S-homo-CAP, and N,N'-dimethyl-4-S-CAP. We tested these five compounds in mice in vivo. After s.c. or i.p. injection of saline solution (in control groups) or one of the compounds, follicular melanocytes were examined by light and electron microscopy to assess the degree of melanocytotoxicity; N-Ac-4-S-CAP induced the most depigmentation (98%), whether given i.p. or s.c. After injection of 4-S-CAP or N-Ac-4-S-CAP, the number of murine B16F10 melanoma colonies formed in the lungs was determined; 4-S-CAP and N-Ac-4-S-CAP were almost equally effective, reducing the colonies to 32 and 25% of mean control, respectively. Metabolic studies of the urine showed 9% of 4-S-CAP and 20% of N-Ac-4-S-CAP injected i.p. were excreted unchanged in 24 h; 1.3% of the N-Ac-4-S-CAP was excreted as 4-S-CAP, indicating some conversion. We conclude that N-Ac-4-S-CAP is a suitable model for developing chemotherapy to treat melanoma characterized by high tyrosinase activity and melanin synthesis.