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Biological Investigations of 6-Azathymine A Thymine Analog^*

William H. Prusoff, William L. Holmes and Arnold D. Welch

( Department of Pharmacology, Schools of Medicine, Western Reserve University, Cleveland, Ohio and Yale University, New Haven, Conn.)

6-Azathymine (3,5-dihydroxy-6-methyl-1,2,4-triazine) competitively inhibited the growth of S. faecalis and L. casei in media supplemented with thymine or thymidine. A significantly greater amount of the analog was required for 50 per cent inhibition of growth in the presence of thymidine than with thymine. In media supplemented with pteroylglutamic acid or synthetic citrovorum factor, 6-azathymine noncompetitively inhibited the growth of S. faecalis. Although azathymine was essentially noninhibitory for Leuconostoc citrovorum growing on a medium containing either thymidine or synthetic citrovorum factor, it completely inhibited the growth of L. leichmannii, not only on thymidine but also on vitamin B₁₂ and pteroylglutamic acid in the absence of exogenous thymidine. The significance of these results for the pathways of thymine and thymidine utilization has been discussed. The compound had no apparent effect on the development of the chick embryo.

^* This investigation was supported in part by a grant from the American Cancer Society, as recommended by the Committee on Growth, National Research Council, and in part by a grant from the National Institutes of Health, U.S. Public Health Service.

A portion of this work was done while this author was a Merck Postdoctoral Fellow of the National Research Council of Canada.

The present address of all authors is Department of Pharmacology, Yale University School of Medicine, New Haven 11, Conn.

Received 4/12/54.