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 bisamidine s (1-3) possessing different dicationic terminal side chains were studied. The ultrafiltration assay showed that bisamidines 1-3 have significant affi nity for DNA, The DNA-binding data for bisamidines 1-3 using homopolymers p oly(dA-dT) poly(dA-dT) and poly(dG-dC) poly(dG-dC), indicated that these co mpounds show moderate specificity for AT base pairs. We studied the cytotox icity 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 sh owed comparable antitumour activity to Hoechst 33258, but were substantiall y 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 > isopr opyl > cyclopentyl), in accord with their increases in DNA affinity, as sho wn by the binding constant values.