DNA-binding activity and cytotoxicity of the extended diphenylfuran bisamidines in breast cancer MCF-7 cells.
The DNA binding properties of three novel extended diphenylfuran bisamidines (1-3) possessing different dicationic terminal side chains were studied. The ultrafiltration assay showed that bisamidines 1-3 have significant affinity for DNA. The DNA-binding data for bisamidines 1-3 using homopolymers poly(dA-dT)- poly(dA-dT) and poly(dG-dC)- poly(dG-dC), indicated that these compounds show moderate specificity for AT base pairs. We studied the cytotoxicity effects of bisamidines 1-3, Hoechst 33258 and DAPI (4',6-diamidino-2-phenylindole) in cultured breast cancer MCF-7 cells. The bisamidines 1-3 showed comparable antitumour activity to Hoechst 33258, but were substantially more cytotoxic compared to DAPI. These data show that in broad terms the cytotoxic potency of bisamidines 1-3 in cultured breast cancer MCF-7 cells decreases with the size of the alkyl group substituent (cyclopropyl>isopropyl>cyclopentyl), in accord with their increases in DNA affinity, as shown by the binding constant values.
Bielawski
K
K
Department of Medicinal Chemistry and Drug Technology, Medical Academy of Białystok, Poland. kbiel@amb.ac.bialystok.pl
Wołczyński
S
S
Bielawska
A
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005663:Furans; D004247:DNA