Jiří Farkaš

2H-1,3-Oxazine-2,6(3H)-dione, a new pyrimidine antimetabolite

Abstract 2H-1,3-Oxazine-2,6(3H)-dione inhibits the growth of Escherichia coli B, the inhibition being complete at a concentration of 10−4M. It may be relieved with uridine, cytidine and partly with uracil. Orotic acid, cytosine, purine bases and purine ribonucleosides show no effect. At a molar ratio of uridine to the inhibitor of 1:2 the inhibition is completely suppressed. 2H-1,3-Oxazine-2,6(3H)-dione is thus a novel inhibitor of the biosynthesis of pyrimidine precursors of nucleic acids.

Mechanism of inhibitory effects of 2,3-dihydro-1,3-6h-oxazine-2,6-dione (3-oxauracil). Biosynthesis of 3-oxauridine phosphates in intact cells and cell-free extracts of Escherichia coli.

Abstract The supernatant fraction of Escherichia coli cells treated with [14C]-2,3-dihydro-1,3-6H-oxazine-2,6-dione ([14C]-3-oxauracil) contains the principal portion of radioactivity in the low molecular weight subfraction. The dominant component of this subfraction is a compound with the properties of 3-oxauridine 5′-monophosphate. The compound is also formed from 3-oxauracil and 5-phosphoribosyl 1-pyrophosphate on incubation with the cell-free extract of E. coli. If this incubation mixture is enriched with adenosine 5′-triphosphate, two further compounds are formed, their properties corresponding to 3-oxauridine 5′-di- and -triphosphates. Treatment of the compound possessing properties of 3-oxauridine 5′-triphosphate with snake venom yielded a non-nucleotide compound with a lower chromatographic mobility than authentic 3-oxauridine. This compound appears to be a ribonucleoside with an open oxazine ring.