HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Synthesis and antitumor activity of cysteinyl-3,4-dihydroxyphenylalanines and related compounds.

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.
AuthorsS Ito, S Inoue, Y Yamamoto, K Fujita
JournalJournal of medicinal chemistry (J Med Chem) Vol. 24 Issue 6 Pg. 673-7 (Jun 1981) ISSN: 0022-2623 [Print] United States
PMID6788955 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Antineoplastic Agents
  • Cysteinyldopa
  • Dihydroxyphenylalanine
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: