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Conjugates of mitomycin C (MMC) with estradiol bezoate and estradiol via glutaric acid (EB-glu-MMC and E-glu-MMC, respectively) were examined for their antitumor activities against P388 leukemia and sarcoma 180. EB-glu-MMC and E-glu-MMC were suspended in 10% (v/v) propylene glycol in saline and administered intraperitoneally to mice bearing P388 leukemia intraperitoneally or to mice bearing sarcoma 180 subcutaneously. The antitumor effect against P388 leukemia was greater in the order MMC&gt;E-glu-MMC&gt;EB-glu-MMC, and only the former two compounds significantly increased life span. On the other hand, EB-glu-MMC and E-glu-MMC showed suppression of sarcoma 180 growth at higher doses close to or better than MMC. In the mixture of 1/15 M phosphate buffer (pH 7.4, ionic strength (mu) adjusted to 0.3 with NaCl)-propylene glycol (9:1, v/v) at 37 degrees C, MMC was released much more slowly from EB-glu-MMC suspension than from E-glu-MMC suspension. With regard to chemotherapy against sarcoma 180, both conjugates were considered to supply MMC slowly but effectively at higher doses.

Antitumor Activities of Conjugates of Mitomycin C with Estradiol Benzoate and Estradiol via Glutaric Acid in Suspension Dosage Form.