Detail of "314-50-1"

Reference

Mass spectrometric identification and quantification of compounds involved in the metabolism of pyrazofurin

Mass spectrometric identification and quantification of compounds involved in the metabolism of pyrazofurin. Roboz, J.; Ohnuma, T. (Mt. Sinai Sch. Med., City Univ. New York, New York, N. Y., USA). Mass Spectrom. Drug Metab., [Proc. Int. Symp.], Meeting Date 1976, 151-65. Edited by: Frigerio, Alberto; Ghisalberti, Emilio L. Plenum: New York, N. Y. (English) 1977. CODEN: 37AIAE. DOCUMENT TYPE: Conference CA Section: 1 (Pharmacodynamics) Gas-chromatog.-mass-spectrometric techniques were developed for the identification and quantification of pyrazofurin (I) [30868-30-5], orotic acid [65-86-1], and orotidine [314-50-1] in human serum and urine. Free I was detected for the 1st time in both the serum and urine of patients receiving the drug. Plasma clearance studies established that the level of I decayed exponentially with a half-life of the distribution phase of approx. 10 min. Urinary excretion yielded only 10% of the total drug administered (in 10 days). Orotic acid and orotidine were pos. identified in urine; quantification revealed that 20-100 mmol of orotic acid and 40-80 mmol of orotiodine were excreted in 8-10 days. Pyrazofurin 5'-phosphate [65446-02-8] was identified for the 1st time in lymphocytes (both T and B type) incubated with I. These findings together with the results of reversal expts. support the assumption that the mode of operation of the drug is the interruption of the conversion of orotidine 5'-monophosphate to UMP in the course of the biosynthesis of pyrimidine nucleotides.

Effects of 6-azauridine on nucleotides, orotic acid, and orotidine in L5178Y mouse lymphoma cells in vitro

Effects of 6-azauridine on nucleotides, orotic acid, and orotidine in L5178Y mouse lymphoma cells in vitro. Janeway, Claude M.; Cha, Sungman (Div. Biol. Med., Brown Univ., Providence, R. I., USA). Cancer Res., 37(12), 4382-8 (English) 1977. CODEN: CNREA8. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) Murine lymphoma L5178Y cells in culture were exposed to 5 mM 6-azauridine (I) [54-25-1] for up to 8 h. The nucleotides in the acid-sol. exts. were detd. by high-pressure liq. chromatog. The concns. of uracil and cytosine nucleotides decreased rapidly in the treated cells. ATP [56-65-5] and ADP [58-64-0] increased steadily, whereas GDP [146-91-8] decreased for a few h before returning to the normal level. Orotic acid [65-86-1] and orotidine [314-50-1], but no detectable amt. of orotidine monophosphate (OMP) [2149-82-8], accumulated in treated cells. In homogenates of the cells harvested from ascitic fluids of mice, the presence of a membrane-bound phosphatase [9013-05-2] with activity for OMP was demonstrated, which may be responsible for the lack of OMP accumulation. When incubated with the homogenate, [7-14C]OMP was converted to [7-14C]orotidine in the absence of inorg. phosphate, but it was converted to [7-14C]orotic acid in the presence of phosphate, suggesting the occurrence of an orotidine phosphorylase. The increase in ATP levels and the rapid decrease in the pyrimidine nucleotides obsd. after treatment with I may be responsible for the observation of W. D. Brenckman et al. (1973) that I potentiates the activity of 1-b-D-arabinofuranosylcytosine only when I is added prior to 1-b-D-arabinofuranosylcytosine.