| Superoxide dismutase catalyzes the destruction of superoxide, O{dollar}sbsp{lcub}2{rcub}{lcub}-{rcub}{dollar}, which is one of the deleterious radicals responsible for radiation damage to cells. Superoxide is also implicated in the development of various forms of cancer. The 1-methylpyridinium and 1-methylquinolinium-2-dithioacetic acid derivatives were found to have both radiation protective and antileukemic activities, and presented the possibility that these activities might be due to the ability to mimic the action of superoxide dismutase. This would require the ability of these compounds to complex copper ions in vivo, an ability which has already been demonstrated (Foye and Patarapanich, 1987). Copper (II) complexes of the bis(methylthio) and methylthio amino derivatives of the pyridinium- and quinolinium-2-dithioacetic acids were prepared. The ability of the complexes to mimic superoxide dismutase, i.e., catalyze the reaction: {dollar}{lcub}rm 2Osbsp{lcub}2{rcub}{lcub}-{rcub} + 2Hsp+ to Hsb2Osb2 + Osb2{rcub}{dollar} was determined, and % activities ranged from 0-28%.; A number of copper complexes of other ligands which are not known to be radioprotectants e.g., guanidines, thioureas, 1,2-dithiol-3-thiones, thiazoles, etc., showed very little to essentially no activity (except one). Also one zinc complex of mercaptoethylguanidine did not show any activity.; So copper complexes of radioprotective and antileukemic 1-methylpyridinium and 1-methylquinolinium-2-dithioacetic acid derivatives have revealed the ability to mimic the action of superoxide dismutase, a copper zinc enzyme. This finding provides a mechanism for explaining both the radiation protection as well as antileukemic activity of the dithioacetic acid derivatives, and provides a new mode by which radiation-protective compounds may act. |
