Electrochemistry of the anticancer agents methotrexate and alpha-difluoromethylornithine in iminium form.
The electrochemical characteristics of the antitumor agents methotrexate and alpha-difluoromethylornithine were determined as their iminium derivatives. Iminium formation from methotrexate is accomplished in vivo via protonation by enzyme. The requisite imine precursor is generated from alpha-difluoromethylornithine by condensation with enzyme containing pyridoxal phosphate. Electroreduction occurs in the range of -0.2 to -0.6 V. The relationship of reduction to structure is discussed. A possible mode of anticancer action involving electron transfer is presented.
Kovacic
P
P
Department of Chemistry, University of Wisconsin-Milwaukee 53201.
Ames
J R
JR
Taylor
E C
EC
Ryan
M D
MD
D055598:Chemical Phenomena; D002621:Chemistry; D000518:Eflornithine / Q000032:analysis*; D004563:Electrochemistry; D006863:Hydrogen-Ion Concentration; D008727:Methotrexate / Q000032:analysis*; D011732:Pyridoxal Phosphate / Q000032:analysis
D011732:Pyridoxal Phosphate; D008727:Methotrexate; D000518:Eflornithine