Experimental and computer graphics simulation analyses of the DNA interaction of 1,8-bis-(2-diethylaminoethylamino)-anthracene-9,10-dione, a compound modelled on doxorubicin.

Abstract The crystal structure of the anthraquinone derivative 1,8-bis-(2-diethylaminoethylamino)-anthracene-9, 10-dione has been established. This compound was prepared as a potential DNA-intercalating agent based on the proven intercalators doxorubicin and mitoxantrone. Its DNA-binding properties have been examined experimentally by spectroscopic, thermal denaturation and ccc-DNA unwinding techniques: the results are consistent with an intercalative mode of binding to DNA. Computer graphics simulation of the intercalative docking of this compound into the self-complementary dimer of d(CpG) has provided a minimum energy geometrical arrangement for the bound drug in the intercalation site comparable to that for proflavine when intercalated into the same d(CpG) model system. Entry of the compound into the site can only occur via the major groove.