SUBSTITUTED 2-ACYLPYRIDINE-ALPHA-(N)-HETARYLHYDRAZONES AS INHIBITORS OF RIBONUCLEOTIDE REDUCTASE-ACTIVITY AND L1210 CELL-GROWTH

A series of substituted 2-acylpyridine-alpha-(N)-hetaryl-hydrazones wa s prepared and studied for their effects on mammalian ribonucleotide r eductase activity using a highly purified enzyme preparation from Ehrl ich tumor cells and on mouse leukemia L1210 cell growth in culture. Py ridine-2-aldehyde-2-pyridylhydrazone (PH 22), ethyl-2-pyridylketone-1- phthalazinylhydrazone (PH 22-25) and pyridine-2-aldehyde-2'-quinolylhy drazone (PQ 22) inhibited purified ribonucleotide reductase activity a nd inhibited L1210 cell growth in culture. PH 22-25 inhibited [H-3]thy midine incorporation into DNA and inhibited ribonucleotide reductase a ctivity in situ (as measured bvy [C-14]cytidine metabolism and as a re sult inhibited DNA synthesis. There was no effect on RNA synthesis. Th ese data indicate that these substituted hydrazones are potent inhibit ors of tumor cell growth through the inhibition of ribonucleotide redu ctase.