Antonie van Leeuwenhoek

, Volume 21, Issue 1, pp 385–396

Chemical and biological studies on 1,2-dihydro-s-triazines

VII. Activity in pteroylglutamic acid-Lactobacillus casei # 7469 systems
  • G. E. Foley
  • E. C. Haley


A series of 1,2-dihydro-s-triazines has been studied inLactobacillus casei # 7469-pteroylglutamic acid systems. The active derivatives exhibit a competitive inhibition similar to that of 4-aminopteroylglutamic acid, but differ from the latter in that inhibition is not relieved by adenine or guanine, and at appropriate concentrations of inhibitor, is not reversed by excess pteroylglutamic acid. Differences in microbiological activity can be correlated with certain alterations in the structure of the molecule, maximum activity being exhibited by the 2,2-dimethyl-phenyl- and 2,2-dimethyl-m-chlorophenyl derivatives.

The inhibitory effect of these compounds is reversed·by appropriate concentrations of dihydropteroylglutamic acid, N10-formylpteroylglutamic acid, synthetic and natural citrovorum factor, thymine and thymidine. The similarity in inhibition indices obtained vs the various forms of pteroylglutamic acid inLactobacillus casei bioassay systems and the correlation with those vs citrovorum factor inStreptococcus faecalis # 8043 andLeuconostoc citrovorum # 8081 bioassay systems suggests that inhibition ofLactobacillus casei is the result of interference with the utilization of citrovorum factor.


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  1. 1.
    Brockman, J. A., Jr., Roth, B., Broquist, H. P., Hultquist, M. E., Smith, J. M., Jr., Rahrenbach, M. J., Cosulich, D. B., Parker, R. P., Stokstad, E. L. R., andJukes, T. H., J. Am. Chem. Soc.72, 4325, 1950.CrossRefGoogle Scholar
  2. 2.
    Curd, F. H. S., andRose, F. L., J. Chem. Soc.1946, 343.Google Scholar
  3. 3.
    Farber, S., Diamond, L. K., Mercer, R. D., Sylvester, R. F., Jr., andWolff, J. A., New Eng. J. Med.238, 787, 1948.CrossRefPubMedGoogle Scholar
  4. 4.
    Farber, S., Diamond, I., Foley, G. E., andModest, E. J., Amer. J. Path.28, 559, 1952.Google Scholar
  5. 5.
    Farber, S., Foley, G. E., Downing, V., Appleton, R., andKing, J., Proc. Amer. Assoc. for Cancer Res.1, 15, 1953.Google Scholar
  6. 6.
    Fildes, P., Lancet1, 955, 1940.CrossRefGoogle Scholar
  7. 7.
    Foley, G. E., andModest, E. J., Proc. 52nd Gen. Meeting, Soc. Amer. Bact., 1952, 63, May 1, Boston, Massachusetts.Google Scholar
  8. 8.
    Foley, G. E., Proc. Soc. Exp. Biol. Med.83, 733, 1953.PubMedGoogle Scholar
  9. 9.
    Foley, G. E., Proc. Soc. Exp. Biol. Med.83, 740, 1953.PubMedGoogle Scholar
  10. 10.
    Foley, G. E., andWatson, P. L., Proc. Soc. Exp. Biol. Med.83, 742, 1953.PubMedGoogle Scholar
  11. 11.
    Foley, G. E., andHaley, E. C., J. Bact.66, 727, 1953.PubMedGoogle Scholar
  12. 12.
    Foley, G. E., Thesis, 1954, Universiteit van Amsterdam.Google Scholar
  13. 13.
    Foley, G. E., andWinter, W. D., Jr., Proc. Amer. Assoc. for Cancer Res.1, 14, 1954.Google Scholar
  14. 14.
    Gordon, M., Ravel, J. M., Eakin, R. E., andShive, W., J. Am. Chem. Soc.70, 878, 1948.CrossRefPubMedGoogle Scholar
  15. 15.
    Green, H. N., Brit. J. Exp. Path.21, 38, 1940.Google Scholar
  16. 16.
    Hewitt, R. I., Wallace, W. S., Gumble, A., White, E., andWilliams, J. H., Amer. J. Trop. Med. Hyg.3, 225, 1954.Google Scholar
  17. 17.
    Hitchings, G. H., Falco, E. A., Van der Werff, H., Russell, P. B., andElion, G. B., J. Biol. Chem.199, 43, 1952.PubMedGoogle Scholar
  18. 18.
    Hitchings, G. H., Maggiolo, A., Russell, P. B., Van der Werff, H., andRollo, I. M., J. Amer. Chem. Soc.74, 3200, 1952.CrossRefGoogle Scholar
  19. 19.
    Hutchings, B. L., Mowat, J. H., Oleson, J. J., Stokstad, E. L. R., Boothe, J. H., Waller, C. W., Angier, R. B., Semb, J., andSubbarow, Y., J. Biol. Chem.170, 323, 1947.Google Scholar
  20. 20.
    Jukes, T. H., andStokstad, E. L. R., Physiol. Rev.28, 51, 1948.PubMedGoogle Scholar
  21. 21.
    Lederle Laboratories Bulletin27, 39, 1952.Google Scholar
  22. 22.
    Lux, R. E., Antibiotics and Chemotherapy4, 971, 1954.Google Scholar
  23. 23.
    McIntosh, J., andWhitby, E. H., Lancet1, 431, 1939.CrossRefGoogle Scholar
  24. 24.
    Modest, E. J., Foley, G. E., Pechet, M. M., andFarber, S., J. Amer. Chem. Soc.74, 855, 1952.CrossRefGoogle Scholar
  25. 25.
    Modest, E. J., Absts. of Papers, 122nd Meeting, Amer. Chem. Soc., 1952, 9L, September 16, Atlantic City, New Jersey.Google Scholar
  26. 26.
    Modest, E. J., Farber, S., andFoley, G. E., Proc. Amer. Assoc. for Cancer Res.1, 33, 1954.Google Scholar
  27. 27.
    Modest, E. J., Foley, G. E., Winter, W. D., Jr., andFarber, S., Proc. Amer. Assoc. for Cancer Res.2, 35, 1955.Google Scholar
  28. 28.
    Modest, E. J., J. Org. Chem.1956, In press.Google Scholar
  29. 29.
    Modest, E. J., andLevine, P., J. Org. Chem.1956, In press.Google Scholar
  30. 30.
    O'Dell, B. L., Vandenbelt, J. M., Bloom, E. S., andPfiffner, J. J., J. Am. Chem. Soc.69, 250, 1947.CrossRefPubMedGoogle Scholar
  31. 31.
    Oleson, J. J., Hutchings, B. L., andSubbarow, Y., J. Biol. Chem.175, 359, 1948.PubMedGoogle Scholar
  32. 32.
    Rudenberg, L., Foley, G. E., andWinter, W. D., Jr., Science121, 899, 1955.PubMedGoogle Scholar
  33. 33.
    Sauberlich, H. E., andBauman, C. A., J. Biol. Chem.176, 165, 1948.PubMedGoogle Scholar
  34. 34.
    Shive, W., andRoberts, E. C., J. Biol. Chem.162, 463, 1946.Google Scholar
  35. 35.
    Stamp, T. C., Lancet2, 10, 1939.CrossRefGoogle Scholar
  36. 36.
    Teply, L. J., andElvehjem, C. A., J. Biol. Chem.157, 303, 1945.Google Scholar
  37. 37.
    Winter, W. D., Jr., andFoley, G. E., To be published.Google Scholar
  38. 38.
    Woods, D. D., Brit. J. Exp. Path.21, 74, 1940.Google Scholar
  39. 39.
    Woolley, D. W., A Study of Antimetabolites, 1952, John Wiley and Sons, Inc., New York, New York.Google Scholar
  40. 40.
    Work, T. S., andWork, E., The Basis of Chemotherapy, 1948, Oliver and Boyd, ltd., Edinburgh, Scotland.Google Scholar

Copyright information

© Boekhandel en Uitgeversmaatschappij 1955

Authors and Affiliations

  • G. E. Foley
    • 1
    • 2
  • E. C. Haley
    • 1
    • 2
  1. 1.Labratoires of MicrobiologyThe Children's Cancer Research FoundationBostonU.S.A.
  2. 2.Department of PathologyHarvard Medical School, at The Children's Medical CenterBostonU.S.A.

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