SYNTHESIS OF NEW ANTITUMOR ANTHRACYCLINES - DERIVATIVES BEARING A FLUORINE SUBSTITUTION AT POSITION 8 OR 10

Concentration of drug bound to nuclear DNA of cancer cells is clearly associated with the main pharmacological effects of the anthracycline aminoglycosides, the molecular mechanism of antitumor activity being i dentified with an interference with the topoisomerase II-DNA complex. Both x-ray diffraction analysis and theoretical computations indicate the presence of a stabilizing hydrogen bond between the 9-OH of the an thracyclines and the amino group and N-3 of a guanine residue in the D NA-drug complex. We have therefore synthesized analogs containing a fl uorine atom at position 8 or 10 with the aim at obtaining derivatives with higher affinity for the typical anthracycline intercalation sites 5'-(A,T)CG-3' or 5'-(A,T)GC-3' in double stranded DNA.