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Novel Mixed-Ligand Copper(I) Complexes: Role of Diimine Ligands on Cytotoxicity and Genotoxicity (Articolo in rivista)

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Novel Mixed-Ligand Copper(I) Complexes: Role of Diimine Ligands on Cytotoxicity and Genotoxicity (Articolo in rivista) (literal)

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Alternative label

Gandin V.; Porchia M.; Tisato F.; Zanella A. ; Severin E. ; Dolmella A. ; Marzano C. (2013)
Novel Mixed-Ligand Copper(I) Complexes: Role of Diimine Ligands on Cytotoxicity and Genotoxicity
in Journal of medicinal chemistry; ACS, American chemical society, Washington, DC (Stati Uniti d'America)
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Gandin V.; Porchia M.; Tisato F.; Zanella A. ; Severin E. ; Dolmella A. ; Marzano C. (literal)

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1,6,7 : Dipartimento di Scienze del Farmaco, Università di Padova, via Marzolo 5, 35131 Padova, Italy / 2,3,4 : IENI-CNR, Corso Stati Uniti 4, 35127 Padova, Italy / 5 : Genetics Department, 'Carol Davila' University of Medicine and Pharmacy, 24, Kiseleff str., RO-011346 Bucharest, Romania (literal)

Titolo

Novel Mixed-Ligand Copper(I) Complexes: Role of Diimine Ligands on Cytotoxicity and Genotoxicity (literal)

Abstract

Novel tetrahedral copper(I) mixed-ligand complexes of the type [Cu(X)(N?N)(PCN)], 3-10, where X = Cl or Br, N?N = 2,2?-bipyridine (bipy), 1,10-phenanthroline (phen), 5,6-dimethyl-1,10-phenanthroline (dmp), and dipyrido-[3,2-d:2?,3?-f]-quinoxaline (dpq), and PCN = tris-(2-cyanoethyl)phosphine, have been synthetized and characterized by NMR, ESI-MS, and X-ray diffraction on two representative examples, [CuCl(phen)(PCN)]·DMF (5·DMF) and [CuBr(dpq)(PCN)]·2DMF (10·2DMF). Cu(I) complexes were evaluated for their in vitro antitumor properties against a panel of human cancer cell lines, including cisplatin- and multidrug-resistant sublines. The most effective complex, [CuCl(dpq)(PCN)] (9), exhibited nanomolar cytotoxicity toward both sensitive and resistant cancer cells, but it significantly inhibited the growth of cultured normal cells. In vitro DNA assays and single cell gel electrophoresis revealed that 9 induced DNA fragmentation resulting in cell apoptosis. In parallel, fluorescence in situ hybridization (FISH) micronucleus assay attested high levels of genotoxicity following treatment of peripheral blood lymphocytes with complex 9, suggesting that the potential risk posed by diimine metal complexes should be carefully reconsidered. (literal)

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