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  • Title: Antitumor activity evaluation of bromine-substituted analogues of ifosfamide. I. Stereodifferentiation of biological effects and selection of the most potent compounds.
    Author: Glazman-Kuśnierczyk H, Matuszyk J, Radzikowski C.
    Journal: Immunopharmacol Immunotoxicol; 1992; 14(4):883-911. PubMed ID: 1294626.
    Abstract:
    The series of 9 compounds, including 3 racemates and 6 enantiomers of bromine-substituted analogues of ifosfamide (bromo-, chlorobromo- and dibromofosfamides) have been evaluated for antitumor activity against L1210 leukemia, Lewis lung carcinoma and B16 melanoma in mice. Effective and curative doses of tested compounds were estimated on the basis of computer-assisted elaboration of the dose-effect curves obtained from experimental data. Two oxazaphosphorine drugs, ifosfamide and its congener cyclophosphamide, were used as referentials. Elementary toxicity studies were conducted in parallel in healthy animals and lethal doses were determined. Selection of the most potent compounds was based on the comparison of their therapeutic indices, calculated from the ratio of lethal to effective doses. In effect four compounds which have been shown therapeutically more effective than both referential drugs, were selected for further evaluation in mice bearing advanced tumours. Stereodifferentiation of evaluated biologic effects favouring S(-) isomers was observed in all three groups of compounds. Preliminary observation was also made indicating significant lethality reduction after per os administration of selected agents, which was not paralleled by diminution of their antitumor effectivity.
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