title: Combined effect of platination and intercalation upon DNA binding of novel cytotoxic Pt-bis(naphthalimide) complexes.
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 (r(b) = 0.025), compounds 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 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.
authors.affiliation: Departamento de Química Inorgánica, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Pérez
authors.forename: I
authors.initials: I
authors.lastname: López-Solera
authors.forename: E I
authors.initials: EI
authors.lastname: Montero
authors.forename: M F
authors.initials: MF
authors.lastname: Brana
authors.forename: C
authors.initials: C
authors.lastname: Alonso
authors.forename: S P
authors.initials: SP
authors.lastname: Robinson
authors.forename: C
authors.initials: C
authors.lastname: Navarro-Ranninger
mesh_terms: D015057:1-Naphthylamine / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D007364:Intercalating Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010984:Platinum / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D007364:Intercalating Agents; D010984:Platinum; D015057:1-Naphthylamine