MOLECULAR MODELING OF INTERCALATION COMPLEXES OF ANTITUMOR ACTIVE 9-AMINOACRIDINE AND A [D,E]-ANELLATED ISOQUINOLINE DERIVATIVE WITH BASE PAIRED DEOXYTETRANUCLEOTIDES

Intercalators are molecules capable of sliding between DNA base pairs without breaking up the hydrogen bonds between the DNA bases. On the b asis of molecular mechanics calculations structural, models of B-DNA t etranucleotide intercalation complexes of some cytostatic active 9-ami noacridines and of a [d, e]-anellated isoquinoline derivative are pres ented. The drug complexes are stabilized by energetically favoured tra it del Waals interactions and by selective hydrogen bonds between the side chains of the drugs and the DNA bases. Semiempirical quantum chem istry calculations revealed that the chromophoric system of the interc alators is able to form pi,pi-charge-transfer interactions with the pu rine bases of the base paired deoxytetranucleotides. The theoretical f indings are of interest for a more specific drug design of cytostatica lly active agents.