teroxirone and Leukemia-P388

The noteworthy cytostatic activity of triglycidyl-s-triazinetrione and the planned clinical testing of this new active substance induced us to subject this class of substances to closer examination. By chemical reaction of one of the three glycidyl groups present it was possible to introduce wide variations in the properties of the compounds, whilst still retaining the active principle. A number of these substances possessed very high antitumor activity as revealed in the leukemia screening test (P 388; mouse). The influence of other substituents within the glycidyl groups affecting the reactivity of the epoxides groups was also examined.

Topics: Animals; Antineoplastic Agents; Biological Assay; Chemical Phenomena; Chemistry; Hydrogen-Ion Concentration; Leukemia P388; Mice; Oxidation-Reduction; Triazines

As a follow-up to our initial results on the antineoplastic activity of alpha-1,3,5-triglycidyl-s-triazinetrione (alpha TGT, NSC-296934, Teroxirone), many new epoxyde derivatives were tested against murine tumours, mostly against P388 leukaemia, to determine their antineoplastic role and to characterize their specific effect against tumour cells in vivo, as well as to select an analogue with higher anti-cancer properties and superior pharmacological properties. Triglycidyl urazol (TGU, NSC-332488) showed the highest therapeutic activity and a good level of water-solubility which makes this agent a good candidate for phase-one clinical trials.

Topics: Animals; Antineoplastic Agents; Cyclophosphamide; Drug Evaluation, Preclinical; Epoxy Compounds; Ethers, Cyclic; Female; Leukemia L1210; Leukemia P388; Mice; Mice, Inbred Strains; Neoplasms; Triazines