Inhibition of deoxyribonucleotide synthesis by pyridine carboxaldehyde thiosemicarbazones.

Abstract

Summary The tumor-inhibitory agent 2-formylpyridine thiosemicarbazone (PT) and its 3- and 5-hydroxy derivatives (3-HP and 5-HP) inhibited the incorporation of cytidine-5-3H into acid-soluble deoxyribonucleotides of Sarcoma 180 cells in vitro. These compounds also inhibited reduction of CDP-32P to dCDP by both a cell-free extract of Sarcoma 180 and a 30-fold purified ribonucleoside diphosphate reductase from the Novikoff rat hepatoma. Fifty % inhibition of these enzyme preparations required approximately 4 × 10-7m PT or 3 to 4 × 10-6m 3-HP or 5-HP. Inhibition of reductase activity by PT was partially reversed by increased concentrations of dithiol substrate but not by increased levels of ferrous ion, whereas inhibitions by 3-HP or 5-HP were partially reversed by ferrous ion but not by the dithiol.