MOLECULAR-STRUCTURE OF THE HALOGENATED ANTICANCER DRUG IODODOXORUBICIN COMPLEXED WITH D(TGTACA) AND D(CGATCG)

4'-Deoxy-4'-iododoxorubicin, a halogenated anthracycline derivative, i s an anticancer agent currently under Phase II clinical trials. In pre clinical studies, it has demonstrated significantly reduced levels of cardiotoxicity compared to currently employed anthracyclines. It also has modified pharmacological properties resulting in an altered spectr um of experimental antitumor activity. The iodine atom at the 4' posit ion of the sugar ring reduces the basicity and enhances the lipophilic ity of this compound as compared to related anthracycline drugs, We re port here single crystal X-ray diffraction studies of the complexes of 4'-deoxy-4'-iododoxorubicin with the hexanucleotide duplex sequences d(TGTACA) and d(CGATCG) at 1.6 and 1.5 Angstrom, respectively. The iod ine substituent does not alter the geometry of intercalation as compar ed to previously solved anthracycline complexes, but appears to marked ly affect the solvent environment of the structures, This could have c onsequences for the interaction of this drug with DNA and DNA binding proteins in cells.