Effects of the stereochemical configuration on the interaction of some daunomycin derivatives with DNA

Four stereoisomeric daunomycin derivatives, characterized by the absence of the methoxyl group in position 4, have been examined for effects on the thermal denaturation of calf thymus DNA and for their ability to bind to DNA, in order to delineate the antibiotic steric features affecting the binding ability. The major conclusions are: (a) the inverted configuration at positions 7 and 9 markedly decreases the DNA binding; (b) the consequences of the above stereochemical inversion are more critical that the inversion of configuration at position 1 of the amino sugar; (c) in general, the effects on the in vitro activity of nucleic acid polymerizing enzymes are consistent with the DNA interaction properties. The structure-activity correlations deduced from these studies are in agreement with earlier findings relating to antitumor activity.