STUDIES ON ANTI-TUMOR ACTIVITIES OF OXIMES AND METAL CHELATE COMPOUNDS

I. EXAMINATIONS OF OXIMES

抄録

The antitumor activities of oximes were examined on Ehrlich ascites carcinoma and Crocker sarcoma 180. 1) Levulinic acid oxime showed a clear antitumor activity at the in vitro test, and a slight inhibitory effect in vivo. This oxime was found to show the destructive actions on cell membranes of the carcinoma at the concentration of 20mg/ml, and to inhibit the activity of dehydrogenase at the concentration of 5mg/ml. The necessary dose of the oxime to destroy the selective permeability of the cell membranes was about five times that of nitromin, and about the same with that of sarkomycin. The LD₅₀ of the oxime was 2040mg/kg (mice, intravenously). 2) The fact that γ-aminovaleric acid and levulinic acid did not show the activity suggested the necessity of the isonitroso group of levulinic acid oxime for the display of the activity. 3) About 20 monoximes and others having structural relationships with levulinic acid oxime were examined for their activities, but none showed the inhibitory actions on the tumors in vivo.
4) α-Ketoglutaric acid oxime was found to be a chelating agent and to form chelates with copper, iron, and nickel at the physiological pH. The injurious action of the oxime on the selective permeability of cell membranes of the tumor was increased in the presence of copper and iron in the forms of its chelate compounds.