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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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Pérez JM,López-Solera I,Montero EI,Brana MF,Alonso C,Robinson SP,Navarro-Ranninger C

doi

10.1021/jm991099r

keywords:

subject

Has Abstract

pub_date

1999-12-30 00:00:00

pages

5482-6

issue

26

eissn

0022-2623

issn

1520-4804

pii

jm991099r

journal_volume

42

pub_type

杂志文章

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