New anthracenedione derivatives: interaction with DNA and biological effects.
Two anthracenedione derivatives [1 - (omega - diethylaminopropylamido) - 4 - hydroxy - 9,10 - anthracenedione hydrochloride (I) and 1 - (omega - diethylaminopropylamido) - 2 - methoxy - 4 - hydroxy - 9, 10 - anthracenedione hydrochloride (II)], having an electron-rich planar chromophore and an amino-substituted side chain, have been synthesized. Their binding ability to DNA was investigated by means of spectroscopic, equilibrium dialysis and fluorescence measurements. Their inhibition efficiency on nucleic acid synthesis was also evaluated both in mouse and human cells. Our results indicate that, in comparison with adriamycin, compound I shows a slightly weaker complexation ability to DNA, while compound II interacts with DNA at a substantially lower level. These data match quite well with the biological response on the inhibition of DNA and RNA synthesis exhibited by the above mentioned compounds; in fact compound I is slightly less efficient than adriamycin and about ten times more efficient than compound II. The close relationship between the results of physicochemical and biological studies is discussed.
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism*; D003956:Dialysis; D004317:Doxorubicin / Q000494:pharmacology; D005453:Fluorescence; D006801:Humans; D051379:Mice; D012313:RNA / Q000096:biosynthesis; D013053:Spectrophotometry
D000880:Anthraquinones; D000903:Antibiotics, Antineoplastic; D012313:RNA; D004317:Doxorubicin; C038733:1-(omega-diethylaminopropylamido)-4-hydroxy-9,10-anthracenedione; C038734:1-(omega-diethylaminopropylamide)-2-methoxy-4-hydroxy-9,10-anthracenedione; D004247:DNA