Quinoline-2-carboxaldehyde thiosemicarbazones and their Cu(II) and Ni(II) complexes as topoisomerase IIa inhibitors.
A series of quinoline-2-carboxaldehyde thiosemicarbazones and their copper(II) and nickel(II) complexes were synthesized and characterized. In all complexes the ligands are in the E configuration with respect to the imino bond and behave as terdentate. The copper(II) complexes form square planar derivatives with one molecule of terdentate ligand and chloride ion. A further non-coordinated chloride ion compensates the overall charge. Nickel(II) ions form instead octahedral complexes with two ligands for each metal ion, independently from the stoichiometric metal:ligand ratio used in the synthesis. Ligands and complexes were tested for their antiproliferative properties on histiocytic lymphoma cell line U937. Copper(II) derivatives are systematically more active than the ligands and the nickel complexes. All copper derivatives result in inhibiting topoisomerase IIa in vitro. Computational methods were used to propose a model to explain the different extent of inhibition presented by these compounds. The positive charge of the dissociated form of the copper complexes may play a key role in their action.
Department of Chemistry, University of Parma, Parco Area delle Scienze 17A, 43124 Parma, Italy; CIRCMSB (Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici), Parma Unit, University of Parma, Italy.
Franco
F
Bisceglie
Department of Chemistry, University of Parma, Parco Area delle Scienze 17A, 43124 Parma, Italy.
Anastasia
A
Musiari
Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126 Parma, Italy; CIRCMSB (Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici), Parma Unit, University of Parma, Italy.
Silvana
S
Pinelli
Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126 Parma, Italy; CIRCMSB (Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici), Parma Unit, University of Parma, Italy.
Rossella
R
Alinovi
Department of Physics and Earth Sciences, University of Parma, Parco Area delle Scienze, 43124 Parma, Italy.
Ilaria
I
Menozzi
Department of Physics and Earth Sciences, University of Parma, Parco Area delle Scienze, 43124 Parma, Italy.
Eugenia
E
Polverini
Department of Chemistry, University of Parma, Parco Area delle Scienze 17A, 43124 Parma, Italy; CIRCMSB (Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici), Parma Unit, University of Parma, Italy.
Pieralberto
P
Tarasconi
Department of Chemistry, University of Parma, Parco Area delle Scienze 17A, 43124 Parma, Italy.
Matteo
M
Tavone
Department of Chemistry, University of Parma, Parco Area delle Scienze 17A, 43124 Parma, Italy; CIRCMSB (Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici), Parma Unit, University of Parma, Italy. Electronic address: giorgio.pelosi@unipr.it.
Giorgio
G
Pelosi
D000447:Aldehydes / Q000737:chemistry*; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry*; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009532:Nickel / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000737:chemistry*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*
C570701:2-quinolinecarboxaldehyde; D000447:Aldehydes; D009942:Organometallic Compounds; D011804:Quinolines; D013882:Thiosemicarbazones; D059005:Topoisomerase II Inhibitors; D003300:Copper; D009532:Nickel; D004250:DNA Topoisomerases, Type II
Copper; Nickel; Quinoline; Thiosemicarbazone; Topoisomerase IIa