Synthesis, DNA-binding activity and cytotoxicity of carbamate derivatives of Hoechst 33258 in breast cancer MCF-7 cells.
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.
Department of Medicinal Chemistry and Drug Technology, Medical Academy of Białystok, Poland. kbiel@amb.edu.pl
Krzysztof
K
Bielawski
Anna
A
Bielawska
Sławomir
S
Wołczyński
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D006690:Bisbenzimidazole / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002219:Carbamates / Q000138:chemical synthesis / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002219:Carbamates; D004247:DNA; D006690:Bisbenzimidazole