Combined Effect of Platination and Intercalation upon DNA Binding of Novel Cytotoxic Pt−Bis(naphthalimide) Complexes

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Abstract
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 chloride, respectively. The testing of the cytotoxic activity of compounds 2 and 3 against several tumor cell lines indicated that both compounds may be endowed with important antineoplastic properties since they circumvent cisplatin resistance. At similar rates of DNA platination (rb = 0.025), compounds 2 and 3 unwind supercoiled pUC8 DNA by (48 ± 2)°. Altogether, these data suggest (i) that the cytotoxic activity of compounds 2 and 3 may be due to a combined effect of platination and intercalation and (ii) that the bis(naphthalimide) ligand is a suitable “carrier” that favors DNA targeting by cis-Pt(II) centers.