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Inhibition of pyrimidine metabolism in myeloid leukemia cells by triazole and pyrazole nucleosides. 1990
S S Matsumoto, and
J M Fujitaki, and
L D Nord, and
R C Willis, and
V M Lee, and
B S Sharma, and
Y S Sanghvi, and
G D Kini, and
G R Revankar, and
R K Robins
Nucleic Acid Research Institute, Costa Mesa, CA 92626.
Two triazole nucleosides, 1 (3-beta-D-ribofuranosyl-1,2,4-triazole-5-carboxamide) and 2 (2-beta-D-ribofuranosyl-1,2,3-triazole-4,5-dicarboxamide), and a pyrazole nucleoside, 3 (1-beta-D-ribofuranosylpyrazole-3,4-dicarboxamide), were found to inhibit pyrimidine nucleotide biosynthesis in the human myeloid leukemia cell line, K562. Cells treated with these inhibitors released orotate in quantities of 8-35 nmol/10(5) cells/day. Treatment with these compounds caused the K562 cells to accumulate in the S phase of the cell cycle and induced the cells to synthesize hemoglobin.
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