Synthesis, DNA-Binding Activity and Cytotoxicity of Carbamate Derivatives of Hoechst 33258 in Breast Cancer MCF-7 Cells

Abstract

A series of carbamate derivatives of Hoechst 33258 was prepared as potential anticancer agents. These new compounds (1—4) were readily prepared in good yields by addition of chloroethyl, bromoethyl, chloropropyl or 4-(chloromethyl)phenyl isocyanates to Hoechst 33258. Their cytotoxic activity was evaluated on human breast cancer MCF-7. Compounds 1—4 were more cytotoxic than Hoechst 33258. In particular derivative 4, the most active of the series, is up to 3 times more potent than Hoechst 33258. The DNA-binding ability of these compounds was evaluated by an ultrafiltration method using calf thymus DNA. These data show that in broad terms the cytotoxic potency of 1—4 in cultured breast cancer MCF-7 cells increases, in accord with their increases in DNA affinity, as shown by the binding constant values.