title: Synthesis, characterization, DNA interaction and cleavage, and in vitro cytotoxicity of copper(II) mixed-ligand complexes with 2-phenyl-3-hydroxy-4(1H)-quinolinone.
abstract: A series of mixed-ligand complexes [Cu(qui)(L)]NO(3)·xH(2)O (1-6), where Hqui = 2-phenyl-3-hydroxy-4(1H)-quinolinone, L = 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), bis(2-pyridyl)amine (ambpy) (3), 5-methyl-1,10-phenanthroline (mphen) (4), 5-nitro-1,10-phenanthroline (nphen) (5) and bathophenanthroline (bphen) (6), have been synthesized and fully characterized. The X-ray structures of [Cu(qui)(phen)]NO(3)·H(2)O (2) and [Cu(qui)(ambpy)]NO(3) (3a) show a slightly distorted square-planar geometry in the vicinity of the central copper(II) atom. An in vitro cytotoxicity study of the complexes found significant activity against human osteosarcoma (HOS) and human breast adenocarcinoma (MCF7) cell lines, with the best results for complex 6, where IC(50) equals to 2.1 ± 0.2 μM, and 2.2 ± 0.4 μM, respectively. The strong interactions of the complexes with calf thymus DNA (CT-DNA) and high ability to cleave pUC19 DNA plasmid were found. A correlation has been found between the in vitro cytotoxicity and DNA cleavage studies of the complexes.
authors.affiliation: Department of Inorganic Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, CZ-771 46, Olomouc, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Buchtík
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Trávníček
authors.forename: Ján
authors.initials: J
authors.lastname: Vančo
authors.forename: Radovan
authors.initials: R
authors.lastname: Herchel
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Dvořák
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D042462:4-Quinolones / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology
chemical_list: D042462:4-Quinolones; C524452:5-nitro-1,10-phenanthroline; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D010618:Phenanthrolines; C017518:5-methyl-1,10-phenanthroline; C006686:bathophenanthroline; D015082:2,2'-Dipyridyl; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; C025205:1,10-phenanthroline; C048062:2,2'-dipyridylamine