title: Human topoisomerase IB is a target of a thiosemicarbazone copper(II) complex.
abstract: The human topoisomerase IB inhibition and the antiproliferative activity of 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone HPyCT4BrPh alone and its copper(II) complex [Cu(PyCT4BrPh)Cl] was investigated. [Cu(PyCT4BrPh)Cl] inhibits both the DNA cleavage and religation step of the enzyme, whilst the ligand alone does not display any effect. In addition we show that coordination to copper(II) improves the cytotoxicity of HPyCT4BrPh against THP-1 leukemia and MCF-7 breast cancer cells. The data indicate that the copper(II) thiosemicarbazone complex may hit human topoisomerase IB and that metal coordination can be useful to improve cytotoxicity of this versatile class of compounds.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Venn
authors.initials: V
authors.lastname: Vutey
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Castelli
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Ilda
authors.initials: I
authors.lastname: D'Annessa
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Luciana B P
authors.initials: LB
authors.lastname: Sâmia
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Souza-Fagundes
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Heloisa
authors.initials: H
authors.lastname: Beraldo
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy. Electronic address: desideri@uniroma2.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Desideri
mesh_terms: D002384:Catalysis; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D004264:DNA Topoisomerases, Type I / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007700:Kinetics; D061986:MCF-7 Cells; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000737:chemistry*
chemical_list: D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C066363:copper-thiosemicarbazone complex; D003300:Copper; D004247:DNA; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human
keywords: Catalytic inhibitor; Copper(II) complex; Cytotoxicity; Human DNA topoisomerase IB; Molecular docking; Thiosemicarbazone