DNA-binding properties and cytotoxicity of extended aromatic bisamidines in breast cancer MCF-7 cells.
The DNA binding properties of three novel extended aromatic bisamidines (1-3) possessing different dicationic terminal side chains were studied. Data from the ethidium displacement assay showed that bisamidines 1-3 have significant affinity for DNA. We studied the cytotoxic activity of bisamidines 1-3 and Hoechst 33258 in the cultured breast cancer MCF-7 cells. These data show that in broad terms the cytotoxic potency of bisamidines 1-3 in the 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. The bisamidines 1-3 showed comparable antitumor activity to Hoechst 33258.
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
D000578:Amidines / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D006690:Bisbenzimidazole / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D014407:Tumor Cells, Cultured
D000578:Amidines; D005456:Fluorescent Dyes; D004247:DNA; D006690:Bisbenzimidazole