title: Copper(II) complexes with substituted thiosemicarbazones of alpha-ketoglutaric acid: synthesis, X-ray structures, DNA binding studies, and nuclease and biological activity.
abstract: New alpha-ketoglutaric acid thiosemicarbazone (H(3)ct) derivatives and their copper complexes were synthesized and characterized by analytical and spectroscopic (IR and NMR) methods. For two of the ligands, Me-H(3)ct and Allyl-H(3)ct, and for a complex, [Cu(Me-Hct)(OH(2))](n) x 2nH(2)O, the X-ray structures were also determined. In the latter the copper atom shows a 4 + 1 pyramidal coordination, a water oxygen appears in the apical position, and three of the basal positions are occupied by the SNO tridentate ligand and the fourth by a carboxylic oxygen of an adjacent molecule that gives rise to a polymeric chain. DNA binding constants were determined, and studies of thermal denaturation profiles and nuclease activity were also performed. Tests in vitro on human leukemia cell line U937 were carried out on cell growth inhibition, cell cycle, and apoptosis induction.
authors.affiliation: Dipartimento di Chimica Generale ed Inorganica, Nefrologia e Scienza della Prevenzione, Università degli Studi di Parma, 43100 Parma, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Baldini
authors.forename: Marisa
authors.initials: M
authors.lastname: Belicchi-Ferrari
authors.forename: Franco
authors.initials: F
authors.lastname: Bisceglie
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Dall'aglio
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pelosi
authors.forename: Silvana
authors.initials: S
authors.lastname: Pinelli
authors.forename: Pieralberto
authors.initials: P
authors.lastname: Tarasconi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004720:Endonucleases / Q000378:metabolism; D006801:Humans; D007656:Ketoglutaric Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D008968:Molecular Conformation; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D007656:Ketoglutaric Acids; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; D003300:Copper; D004247:DNA; D004720:Endonucleases