DNA minor groove cleaving agents: synthesis, binding and strand cleaving properties of anthraquinone-oligopyrrolecarboxamide hybrids.

Three 9,10-anthraquinone-oligopyrrolecarboxamide hybrids have been prepared as potential DNA minor groove cleaving agents. Each conjugate was designed to contain a bis- or tris-pyrrolecarboxamide moiety related to netropsin or distamycin covalently linked to a 2-substituted anthraquinone chromophore capable of triggering photocleavage of DNA. AQ(NC)-Dist, having three pyrrole rings, is related to distamycin. AQ(NC)-Net and AQ(CN)-Net are related to netropsin; they differ only by the orientation of the amide bond between the anthraquinone and the netropsin moiety. The binding properties of these compounds to various natural DNAs have been studied by footprinting and circular dichroism. The introduction of the chromophore does not abolish the capacity of the drugs to recognize AT-rich sequences in DNA selectively. There is apparently little correlation between this property and the ability to trigger photo-induced DNA cleavage. AQ(CN)-Net is almost totally inactive in the cleavage assays whereas it manifestly binds selectively to AT-rich tracts. With AQ(NC)-Net and AQ(NC)-Dist, complete conversion of form I to form II of circular DNA is obtained. Moreover, in most cases the cleavage of DNA proved to be non-specific.