In vitro antineoplastic activity of C7-substituted mitomycin C analogues MC-77 and MC-62 against human breast-cancer cell lines
Cancer Chemotherapy and Pharmacology
A GhiorghisR Clarke
Mitomycin C (MIT-C) is one of the most potent antineoplastic agents used for the treatment of breast cancer and a wide variety of malignant tumors. However, administration of MIT-C is frequently accompanied by the delayed onset of severe myelosuppression We have synthesized a new series of MIT-C analogues that are predicted on a structure/function basis to retain cytotoxicity but exhibit decreased toxicity. These new compounds feature a sugar substitution at the N7 position. Using a series of human breast-cancer cell lines growing in vitro, we determined the structure/activity relationship of two independent N7-substituted spacers displaying the same glucopyranose moiety. N-( [(2-acetamide-3,4,6-tri-O-acetyl-2-deoxy-beta- D-glucopyranosyl)amino]carbonyl] propylmitomycin C (MC-62) contains the sugar moiety linked to MIT-C through a butanoic acid spacer. MC-62 exhibits significantly less biological potency as compared with the parent drug. In contrast, N-[4-(tetra-O-acetylglucopyranosyl)oxy]phenylmitomycin C (MC-77) contains the glucopyranose moiety linked to MIT-C through a phenolic spacer. This analogue generally exhibits greater antitumor activity in vitro as compared with either MC-62 or MIT-C. Thus, N7-substituted analogues ...Continue Reading
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