RT Journal Article
SR Electronic
T1 Studies of the Reaction of 2-Formylpyridine Thiosemicarbazone and Its Iron and Copper Complexes with Biological Systems
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 89
OP 98
VO 13
IS 1
A1 WILLIAM ANTHOLINE
A1 JUDITH KNIGHT
A1 HARRY WHELAN
A1 DAVID H. PETERING
YR 1977
UL http://molpharm.aspetjournals.org/content/13/1/89.abstract
AB The interactions of 2-formylpyridine thiosemicarbazone with various biochemical systems have been studied to understand the potential behavior of this antitumor agent in vivo. This ligand removes iron from ferritin to form the iron(III) complex. The complex is rapidly reduced by hemoglobin and is only slowly reoxidized by oxygen in aqueous solution or plasma. Both the iron(III) and iron(II) chelates are stable in plasma. These results suggest that the iron(II) complex exists in vivo. However, the thermodynamic stability of the copper complex is also consistent with its formation in biological systems. Electron paramagnetic resonance spectra show that in plasma two adduct species of the copper complex form. One of these may involve histidine. Reaction of the ligand or its iron, copper, or zinc complex with the assay mixture used for ribonucleoside diphosphate reductase produces in each case the iron(II) complex of the ligand. These results are used to interpret a number of observations on the physiological effects of α-N-formyl heterocyclic thiosemicarbazones as well as some features of the inhibition of ribonucleoside diphosphate reductase by these compounds.