Melanocytotoxicity and antimelanoma effects of phenolic amine compounds in mice in vivo
- Univ. of Alberta, Edmonton (Canada)
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.
- OSTI ID:
- 6742404
- Journal Information:
- Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 50:12; ISSN 0008-5472; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560300* -- Chemicals Metabolism & Toxicology
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AROMATICS
BIOLOGICAL EFFECTS
CHEMICAL PREPARATION
CHEMOTHERAPY
COLONY FORMATION
DISEASES
DRUGS
EXPERIMENTAL NEOPLASMS
HYDROXY COMPOUNDS
IN VIVO
INHIBITION
INJECTION
INTAKE
INTRAPERITONEAL INJECTION
MAMMALS
MELANIN
MELANOMAS
MICE
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHENOLS
PIGMENTS
RODENTS
SUBCUTANEOUS INJECTION
SYNTHESIS
THERAPY
TUMOR CELLS
VERTEBRATES