Antibiotics pp 451-456 | Cite as


  • Harold T. Shigeura


In addition to certain normal cellular metabolites that exert control over the biosynthesis of nucleic acids, a large number of substances synthesized chemically or obtained from natural sources have now been demonstrated to interfere with the ultimate formation of these macro-molecules. These inhibitors, which are structurally related to purines, pyrimidines and amino acids, have been found to antagonize the metabolism of a corresponding normal substrate. Furthermore, the modes of action of some of these antimetabolites have been elucidated. This review pertains to hadacidin, a structural analogue of L-aspartic acid, isolated from the fermentation fluid of Penicillium frequentans and subsequently found to inhibit the biosynthesis de novo of adenylic acid.


Adenylic Acid Ehrlich Ascites Tumor Cell Propionate Sodium Preliminary Clinical Trial Ehrlich Ascites Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Dixon, G. J., M. M. Blackwell, and F. M. Schabel: Hadacidin potentiation of lethal action of ionizing irradiation. I. Effect of mammalian tumor cells in culture. Proc. Soc. Exptl. Biol. Med. 118, 521 (1965).CrossRefGoogle Scholar
  2. Dulaney, E. L., and R. A. Gray: Penicillia that make N-formylhydroxyaminoacetic acid, a new fungal product. Mycologia 54, 476 (1962).CrossRefGoogle Scholar
  3. Ellison, R. R.: Preliminary clinical trials of hadacidin, a new tumor-inhibitory substance. Clinical Pharm. and Therap. 4, 326 (1963).Google Scholar
  4. Ellison, R. R.: Clinical pharmacologic study of hadacidin (Nsc-521778). Cancer Chemotherapy Reports 46, 37 (1965).Google Scholar
  5. Gitterman, C. O., E. L. Dulaney, E. A. Kaczka, D. Hendlin, and H. B. Woodruff: The human tumor-egg host system. II. Discovery and properties of a new antitumor agent, hadacidin. Proc. Soc. Exptl. Biol. Med. 109, 852 (1962).CrossRefGoogle Scholar
  6. Gray, R. A., G. W. Gauger, E. L. Dulaney, E. A. Kaczka, and H. B. Woodruff: Hadacidin, a new plant-growth inhibitor produced by fermentation. Plant Physiol. 39, 204 (1964).PubMedCrossRefGoogle Scholar
  7. Harris, J. J., M. N. Teller, E. Yap-Guevara, and G. W. Woolley: Effects of hadacidin on human tumors grown in eggs and rats. Proc. Soc. Exptl. Biol. Med. 110, 1 (1962).CrossRefGoogle Scholar
  8. Kaczka, E. A., C. O. Gitterman, E. L. Dulaney, and K. Folkers: Hadacidin, a new growth-inhibitory substance in human tumor systems. Biochem. 1, 340 (1962).CrossRefGoogle Scholar
  9. Lineweaver, H., and D. Burk: The determination of enzyme dissociation constants. J. Am. Chem. Soc. 56, 658 (1934).CrossRefGoogle Scholar
  10. Mego, J. L.: The effect of hadacidin on chloroplast development in non-dividing euglena cells. Biochim. et Biophys. Acta 79, 221 (1964).Google Scholar
  11. Merker, P. C., J. S. Sarino, R. Anido, M. Bowie, and G. W. Woolley: Effect of hadacidin on a transplantable human epidermoid carcinoma. In: J. E. Sylvester (ed.), Antimicrobial Agents and Chemotherapy, p. 749. Ann Arbor (Michigan): Braun-Brumfield, Inc. 1963.Google Scholar
  12. Neuman, R. E., and A. A. Tytell: Inhibitory effects of hadacidin on KB cell cultures. Proc. Soc. Exptl. Biol. Med. 112, 57 (1963).CrossRefGoogle Scholar
  13. Pittillo, R. F., and F. C. Moncrief: Hadacidin potentiation of lethal action of ionization irradiation. II. Effect of proliferating Gram-negative bacteria. Proc. Soc. Exptl. Biol. Med. 118, 525 (1965).CrossRefGoogle Scholar
  14. Shigeura, H. T.: 6-Azauracil inhibition of Escherichia coli B and its reversal by hadacidin. Arch. Biochem. Biophys. 100, 472 (1963a).PubMedCrossRefGoogle Scholar
  15. Shigeura, H. T.: Structural modifications of hadacidin and their effects on the activity of adenylosuccinate synthetase. J. Biol. Chem. 238, 3999 (1963 b).Google Scholar
  16. Shigeura, H. T., and C. N. Gordon: Hadacidin, a new inhibitor of purine biosynthesis. J. Biol. Chem. 237, 1932 (1962a).PubMedGoogle Scholar
  17. Shigeura, H. T., and C. N. Gordon: The mechanism of action of hadacidin. J. Biol. Chem. 237, 1937 (1962b).PubMedGoogle Scholar
  18. Shigeura, H. T., and C. N. Gordon: Further studies on the activity of hadacidin. Cancer Research 22, 1356 (i 962c).Google Scholar
  19. Shull, K. H.: Hepatic phosphorylase and adenosine triphosphate levels in ethioninetreated rats, J. Biol. Chem. 237, PC 1735 (1962).Google Scholar
  20. Shull, K. H., and S. Villa-Trevino: The effects of hadacidin and inosine on hepatic protein synthesis and adenosine triphosphate levels in ethionine-treated rats. Biochem. Biophys. Research. Commun. 16, 101 (1964).CrossRefGoogle Scholar
  21. Villa-Trevino, S., K. H. Shull, and E. Farber: The role of adenosine triphosphate deficiency in ethionine-induced inhibition of protein synthesis. J. Biol. Chem. 238, 1757 (1963).Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1967

Authors and Affiliations

  • Harold T. Shigeura

There are no affiliations available

Personalised recommendations