Antitumor activity of a large number of nitrofuran derivatives of quinoline was tested with mice bearing Ehrlich ascites tumor EY-33. Pure strain healthy
ddN mice, weighing 18-22g., were intraperitoneally inoculated with this Ehrlich ascites tumor. After 24 hours, 0.2ml. of 5% glucose solution of the test compound was injected intraperitoneally, once a day for 7 days, to test antitumor activity. Normal mice inoculated with this ascites tumor generally died from accumulation of the ascites after about 10-19 days. Compounds were considered effective when the mice survived 50 days after the inoculation of the ascites. The compounds found to be effective by this test were sodium 2-[2-(5-nitro-2-furyl)vinyl]-4-quinolinecarboxylate (I), 2-[2-(5-nitro-2-furyl)-vinyl]-4-aminoquinoline lactate (II), and 4-[2-(5-nitro-2-furyl)vinyl]-2-aminoquinoline lactate (III). For the sake of comparison, panfuran hydrochloride and mitomycin-C were tested at the same time.
The data obtained with these compounds were as follows (given in the order of the name of compound, LD
50 in mg./kg., ED
60 in mg.×kg., and C. I.): I, 240, 20, 12; II, 23.8, 1, 23.8; III, 26.3, 5, 5.2; panfuran hydrochloride, 72.5, 0, 0; mitomycin-C, 5.2, 0.5, 12.4.
In order to clarify the action mechanism of these compounds, their action in suppressing the dehydronase of Ehrlich ascites tumor, and syntheses of nucleic acid and protein by
coli bacilli was examined. It was presumed from its results that the antitumor action of I was due mainly to the suppression of dehydrogenase action, and that of II and III to the suppression of dehydrogenase action and DNA synthesis.
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