Competitive fluorescence polarization study of the binding of 1,4-dihydroxy-5,8-bis[(2-[(2-hydroxyethyl) amino] ethyl]amino] 9-10-anthracenedione to DNA.
The title compound is now undergoing Phase I clinical trials as an experimental antitumor agent. Fluorescent polarization was used to determine the extent of inhibition of the binding of acridine orange to DNA. Displacement of 50% of the acridine orange was achieved by 0.21 microM of the title compound, 0.32 microM daunorubicin, 0.41 microM doxorubicin, 0.61 microM dactinomycin, and 7.8 microM cis-platinum. Binding inhibition was essentially equivalent with natural DNAs (calf thymus and Micrococcus luteus) and synthetic polymers [poly d(A):d(T) and poly d(G):d(C)] of widely differing adenine plus thymidine content.
D000165:Acridine Orange / Q000378:metabolism; D000873:Anthracenes / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism*; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D003609:Dactinomycin / Q000378:metabolism; D003630:Daunorubicin / Q000378:metabolism; D004317:Doxorubicin / Q000378:metabolism; D005454:Fluorescence Polarization; D008837:Micrococcus / Q000378:metabolism; D008942:Mitoxantrone
D000873:Anthracenes; D000970:Antineoplastic Agents; D004269:DNA, Bacterial; D003609:Dactinomycin; D004317:Doxorubicin; D004247:DNA; D008942:Mitoxantrone; D000165:Acridine Orange; D003630:Daunorubicin