[Antineoplastic activity and toxicity of dihydroambazone in comparison with ambazone (1,4-benzoquinone-guanylhydrazone-thiosemicarbazone)].
Dihydroambazone 1, a soluble derivative of ambazone, was tested with an admixture of ascorbic acid (0.1, 0.25, or 0.5% in distilled water) for antineoplastic activity by different routes (i.p., p.o., s.c., i.v.) against leukemia P388, and by s.c. application against Lewis lung carcinoma on B6D2F1-mice. The results were compared with that of ambazone. 1 was as active as ambazone upon the per os d 1-4 schedule only. Ascorbic acid, added for stabilization of 1, had no significant influence on the results. Intravenously given 1 was of low activity. It proved to be toxic at 100 mg/kg body mass. The i.v. toxicity was estimated approximately on B6D2F1-mice (LD50: 150 mg/kg; LD100: 175 mg/kg; maximum tolerated dose (MTD): 100 mg/kg. A comparison between the MTD's of 1 and ambazone in mice and rats (Wistar) showed partly a somewhat better p.o. compatibility of 1. The expectation of a favourable i.v. applicable derivative from the otherwise in water nearly insoluble ambazone could not be realized.
Gutsche
W
W
Akademie der Wissenschaften der DDR.
Härtl
A
A
Baumgart
J
J
Schulze
W
W
D000818:Animals; D000970:Antineoplastic Agents; D007928:Lethal Dose 50; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008935:Mitoguazone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; C058853:dihydroambazone; C037931:1,4-benzoquinone guanylhydrazone thiosemicarbazone; D008935:Mitoguazone
Antineoplastische Wirksamkeit und Toxizität von Dihydroambazon im Vergleich zu Ambazon (1,4-Benzochinon-guanylhydrazon-thiosemicarbazon).