Substituted 2-acylpyridine-alpha-(N)-hetarylhydrazones as inhibitors of ribonucleotide reductase activity and L1210 cell growth.
A series of substituted 2-acylpyridine-alpha-(N)-hetarylhydrazones was prepared and studied for their effects on mammalian ribonucleotide reductase activity using a highly purified enzyme preparation from Ehrlich tumor cells and on mouse leukemia L1210 cell growth in culture. Pyridine-2-aldehyde-2-pyridylhydrazone (PH 22), ethyl-2-pyridylketone-I-phthalazinylhydrazone (PH 22-25) and pyridine-2-aldehyde-2'-quinolylhydrazone (PQ 22) inhibited purified ribonucleotide reductase activity and inhibited L1210 cell growth in culture. PH 22-25 inhibited [3H]thymidine incorporation into DNA and inhibited ribonucleotide reductase activity in situ (as measured bvy [14C]cytidine metabolism and as a result inhibited DNA synthesis. There was no effect on RNA synthesis. These data indicate that these substituted hydrazones are potent inhibitors of tumor cell growth through the inhibition of ribonucleotide reductase.
Cory
J G
JG
Department of Biochemistry, East Carolina University School of Medicine Greenville, NC 27858.
Downes
D L
DL
Cory
A H
AH
Schaper
K J
KJ
Seydel
J K
JK
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D006835:Hydrazones / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000473:pathology*; D051379:Mice; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D006835:Hydrazones; D004247:DNA; D012264:Ribonucleotide Reductases