Combined effect of platination and intercalation upon DNA binding of novelcytotoxic Pt-bis(naphthalimide) complexes

The reaction of platinum salts with bis(naphthalimide), compound 1, yielded two Pt-bis-(naphthalimide) complexes, compounds 2 and 3 which differ from each other in their leaving groups being 1,1-cyclobutane dicarboxylate or c hloride, respectively. The testing of the cytotoxic activity of compounds 2 and 3 against several tumor cell lines indicated that both compounds may b e endowed with important antineoplastic properties since they circumvent ci splatin resistance. At similar rates of DNA platination (r(b) = 0.025), com pounds 2 and 3 unwind supercoiled pUC8 DNA by (48 +/- 2)degrees. Altogether , these data suggest (i) that the cytotoxic activity of compounds 2 and 3 m ay be due to a combined effect of platination and intercalation and (ii) th at the bis(naphthalimide) ligand is a suitable "carrier" that favors DNA ta rgeting by cis-Pt(II) centers.