mitoguazone and dihydroambazone

Dihydroambazone (DHA) is a water-soluble derivative of the experimental anticancer drug ambazone. In vitro, a combination of DHA and human recombinant tumor necrosis factor alpha (TNF) exerted a strong synergism of cytotoxicity against both mouse melanoma B16K cells and the TNF-sensitive mouse fibroblast line L-M (S). Furthermore, in a colony-forming assay with B16K cells a combination of TNF and DHA inhibited colony-formation much more severely than either drug alone. An increased antiproliferative efficiency was also confirmed in vivo against established subcutaneous melanoma B16 tumors of C57BL/6 mice.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Colony-Forming Units Assay; Drug Synergism; Female; Humans; Male; Melanoma, Experimental; Mice; Mice, Inbred Strains; Mitoguazone; Neoplasm Transplantation; Random Allocation; Recombinant Proteins; Time Factors; Tumor Necrosis Factor-alpha

The oxidation of dihydroambazone (1) by oxygen is dependent on the pH-values of the solutions used. This transformation can be inhibited and excluded, respectively, by ascorbic acid using defined concentrations. The oxidation product ambazone (2) was determined spectroscopically at different pH-values. The rate of transformation in serum depends on the temperature and can also be inhibited with ascorbic acid.

Topics: Animals; Ascorbic Acid; Biotransformation; Hydrogen-Ion Concentration; Mitoguazone; Oxidation-Reduction; Rats; Temperature

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.

Topics: Animals; Antineoplastic Agents; Lethal Dose 50; Leukemia P388; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred Strains; Mitoguazone; Rats; Rats, Inbred Strains

The influence of 1,4-benzoquinone-guanylhydrazone-thio-semicarbazone (1; ambazone), toluquinone-guanylhydrazone-thiosemicarbazone (2; ambazone 82/80) and p-(thio-semicarbacido)-diaminomethylenehydrazino benzene (3; dihydroambazone) on phytomitogen induced stimulation processes of human lymphocytes was studied. Con A- or PHA-stimulated lymphocytes of healthy probands were treated in vitro with the drugs and the DNA synthesis rate was evaluated by the use of the 3H-labelled thymidine incorporation. A concentration dependent inhibition of the DNA synthesis rate in a comparable quantity for all the tested drugs was found. DNA synthesis was inhibited nearly completely by drug application in a concentration range of 10(-4) mol/l. To check for a possible interference of mitogen stimulation and drug action, 3 was added to the lymphocyte cultures either together with PHA, prior to or after addition of the mitogen. Experiments showed, the sooner the drug acted on the stimulation process, the stronger the DNA synthesis was inhibited.

Topics: Concanavalin A; DNA; Humans; In Vitro Techniques; Lymphocyte Activation; Lymphocytes; Mitoguazone; Phytohemagglutinins; Thymidine

Important properties of p-(thiosemicarbazido)diamino-methylen-hydrazino benzene (1; dihydroambazone) are described. The transformation of this compound into 1,4-benzoquinone guanylhydrazone thiosemicarbazone (2; ambazone) dependent on different aqueous buffer systems was investigated. The spectroscopic behaviour of the transformation product allows us to determine the content of the compound in aqueous solutions, whereas the determination in serum is much more difficult. Furthermore, TLC experiments and oxidation methods are described.

Topics: Chemical Phenomena; Chemistry; Chromatography, Thin Layer; Humans; Hydrogen-Ion Concentration; Mitoguazone; Oxidation-Reduction; Solvents; Spectrophotometry, Ultraviolet