Inhibition of pyrimidine metabolism in myeloid leukemia cells by triazole and pyrazole nucleosides.
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.
Matsumoto
S S
SS
Nucleic Acid Research Institute, Costa Mesa, CA 92626.
Fujitaki
J M
JM
Nord
L D
LD
Willis
R C
RC
Lee
V M
VM
Sharma
B S
BS
Sanghvi
Y S
YS
Kini
G D
GD
Revankar
G R
GR
Robins
R K
RK
D000255:Adenosine Triphosphate / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D006160:Guanosine Triphosphate / Q000378:metabolism; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007291:Inosine Monophosphate / Q000378:metabolism; D007399:Interphase / Q000187:drug effects; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology; D015394:Molecular Structure; D009963:Orotic Acid / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D011742:Pyrimidine Nucleotides / Q000096:biosynthesis*; D012254:Ribavirin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012263:Ribonucleosides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014544:Uridine Triphosphate / Q000096:biosynthesis
D006454:Hemoglobins; D011720:Pyrazoles; D011742:Pyrimidine Nucleotides; D012263:Ribonucleosides; C062999:2-ribofuranosyl-1,2,3-triazole-4,5-dicarboxamide; C063000:1-ribofuranosylpyrazole-3,4-dicarboxamide; D007291:Inosine Monophosphate; D012254:Ribavirin; D009963:Orotic Acid; C062998:3-ribofuranosyl-1,2,4-triazole-5-carboxamide; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D007168:IMP Dehydrogenase; D014544:Uridine Triphosphate