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Amino Acids

, Volume 4, Issue 3, pp 287–302 | Cite as

The effects of boron containing peptides on L1210 lymphoid leukemia metabolism

  • I. H. Hall
  • E. S. Hall
  • M. C. MillerIII
  • A. Sood
  • B. F. Spielvogel
Article
  • 85 Downloads

Summary

The purpose of this study was to establish the efficacy and mode of action of peptide boron derivatives as antineoplastic agents and to evaluate their safety in vivo. Boron-containing phenylalanine and tyrosine methyl esters were found to be potent cytotoxic agents in a number of murine and human cancer cell lines. DNA, RNA and protein syntheses were inhibited by selected agents, e.g. [(trimethylamine boryl)carbonyl]-phenylalanine-acetyl ester (9) andN-acetyl-p-boron-phenyl-alanyl-phenlalanine-methyl ester (10), in L1210 lymphoid leukemia cells. IMP dehydrogenase, OMP decarboxylase, m-RNA, t-RNA, r-RNA polymerase and ribonucleoside reductase activities were inhibited. d(CTP) levels were reduced. DNA strand scission occurred after 24 hr incubation. Acute toxicity studies in mice demonstrated that the key derivative was safe at therapeutic levels with no effects on histology of major organs, hematopoietic parameters and clinical values.

Keywords

Amino acids Antineoplastic agents Boron peptide methyl esters Cytotoxicity L1210 leukemia 

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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • I. H. Hall
    • 1
  • E. S. Hall
    • 1
  • M. C. MillerIII
    • 1
  • A. Sood
    • 2
  • B. F. Spielvogel
    • 2
  1. 1.Division of Medicinal Chemistry and Natural ProductsUniversity of North Carolina at Chapel HillUSA
  2. 2.Boron Biologicals, IncRaleighUSA

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