A note on in vitro inhibition of thymine degradation by some pyrimidine analogues and related products.

Thymine and uracil have been shown to be rapidly catabolized by animal tissues in vitro and in vivo 1_4. Several 5-substituted halogen derivatives of uracil have also been reported to be degraded in the identical manner 5_8. S e b e s t a and coworkers 9 found that 5-substituted nitroand bromouracil inhibit the degradation of thymine and uracil by rat liver acetone powder. In a previous rep o rt10, we have shown that the presence of dihydrouracil and /5-ureidopropionic acid inhibits the degradation of analogous dihydrothymine and /?-ureidoisobutyric acid formed from thymine by pig liver enzyme preparations resulting in their accumula­ tion in the incubation mixtures. In the present work we have examined a number of substituted pyrimidines and related compounds as po­ tential inhibitors of thymine catabolism using partially purified pig liver enzyme preparations. Out of 30 com­ pounds tested, only 7, all 5-substituted uracil deriva­ tives, exhibited a marked inhibitory effect on the degra­ dation of thymine at equimolar ratio of substrate and its analogues.