Biological & Pharmaceutical Bulletin 2002-07-01

Synthesis, DNA-binding activity and cytotoxicity of carbamate derivatives of Hoechst 33258 in breast cancer MCF-7 cells.

Krzysztof Bielawski, Anna Bielawska, Sławomir Wołczyński

Index: Biol. Pharm. Bull. 25(7) , 916-9, (2002)

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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.