Combined effect of platination and intercalation upon DNA binding of novel cytotoxic 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 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.
Pérez
J M
JM
Departamento de Química Inorgánica, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
López-Solera
I
I
Montero
E I
EI
Brana
M F
MF
Alonso
C
C
Robinson
S P
SP
Navarro-Ranninger
C
C
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
D004273:DNA, Neoplasm; D007364:Intercalating Agents; D010984:Platinum; D015057:1-Naphthylamine