Comparative Computer Graphics and Solution Studies of the DNA Interaction of Substituted Anthraquinones Based on Doxorubicin and Mitoxantrone

Article abstract of DOI:10.1021/jm00145a003

1-<<(Diethylamino)ethyl>amino>- and 1,4-, 1,5-, and 1,8-bis<<(diethylamino)ethyl>amino>anthraquinones are shown to intercalate into DNA.Computer graphics modelling of their intercalation into the self-complementary deoxydinucleoside d(CpG) showed differences in binding properties.While the 1-substituted compound can bind from euther groove, the 1,8-disubstituted compound binds with both substituents in the major groove.In the-low energy state of the complex with the 1,5-disubstituted compound, this ligand "straddles" the site with a substituent in each groove-to do this, the compound must bind to a non-base-paired region, so inducing base pairing.The 1,4-compound binds from the major groove; "straddling" is also possible if full minimization of deoxydinucleoside geometry is performed.The differences in binding mode and interaction energies are reflected in the affinities of interaction (1,5- > 1,4- >> 1,8- > 1-); also the antiproliferative effects in vitro are in general agreement with this ranking.