Abstract |
The natural catecholic amino acid 5-S-cysteinyl-3,4-dihydroxyphenylalanine (1) was selectively toxic to a variety of human tumor cell lines in culture and exhibited antitumor activity against L1210 leukemia and B-16 melanoma in mice at doses which were not toxic to the host. Structural analogues of 5-S-cysteinyl-3,4-dihydroxyphenylalanine including several new compounds, were synthesized and tested for growth inhibition of cultured cells of human neuroblastoma YT-nu and Chinese hamster fibroblasts Don-6. Some were also examined for antitumor activity against L1210 and B-16 in vivo. 4-S-Cysteinylcatechols and 2- and 4-S-cyteinylphenols, which cannot be prepared by conventional methods, were synthesized by the reaction of catechols and phenols with cystine and boiling aqueous HBr. 5-S-Cysteinyl- and 2-S-Cysteinyl-3,4-dihyroxyphenylalanine (1 and 2), L-3,4-dihydroxyphenylalanine ( L-Dopa), and 2- and 4-S-cysteinylphenol (14 and 15) were toxic to the YT-nu cell line only, while 4-S-cysteinylcatechol (6), 3-S-cysteinyl-5-methylcatechol (8), 5-S-cysteaminyldopamine (9), and 4-methylcatechol were strongly toxic to both cell lines. Compound I (1000 mg/kg), 6 (500 mg/kg), and 8 (400 mg/kg) increased the life span of L1210-bearing mice by 50, 50, and 43%, respectively, and compounds 1 and 8 were marginally effective against B-16 melanoma as well. Compound 9 was too toxic to show any activity. There was a good correlation between the cytotoxicity and the in vivo activity.
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Authors | S Ito, S Inoue, Y Yamamoto, K Fujita |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 24
Issue 6
Pg. 673-7
(Jun 1981)
ISSN: 0022-2623 [Print] United States |
PMID | 6788955
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Antineoplastic Agents
- Cysteinyldopa
- Dihydroxyphenylalanine
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Topics |
- Animals
- Antineoplastic Agents
- Cell Division
(drug effects)
- Cell Line
- Cricetinae
- Cysteinyldopa
(analogs & derivatives, chemical synthesis, pharmacology)
- Dihydroxyphenylalanine
(analogs & derivatives)
- Humans
- Leukemia L1210
(drug therapy)
- Male
- Melanoma
(drug therapy)
- Mice
- Neoplasms, Experimental
(drug therapy)
- Neuroblastoma
(drug therapy)
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