title: Structural diversity of copper(II) complexes with N-(2-pyridyl)imidazolidin-2-ones(thiones) and their in vitro antitumor activity.
abstract: Six series of structurally different mono- and binuclear copper(II) complexes 5-10 were obtained by reacting N-(2-pyridyl)imidazolidin-2-ones (1a-l), N,N'-bis(2-pyridyl)imidazolidin-2-ones (2a,b), N-acyl-N'(2-pyridyl)imidazolodin-2-ones (3a-j) and N-(2-pyridyl)imidazolidine-2-thiones (4a-g) with copper(II) chloride at an ambient temperature. The coordination modes of the complexes obtained were established by elemental analysis, IR spectroscopic data and single crystal X-ray diffraction studies. The in vitro cytotoxic activities of both the free ligands and copper(II) complexes were evaluated using a crystal violet microtiter plate assay on five human tumor cell lines: LCLC-103H, A-427, SISO, RT-4 and DAN-G. The free ligands 1-4 at concentration attainable in cancer cells of 20 μM showed no meaningful cytotoxic effect with cell viability in the range of 88%-100%. The most potent copper(II) complex of 1-(6-ethoxy-2-pyridyl)imidazolidin-2-one (6b) exhibited selective cytotoxicity against A-427 lung cancer cell line, while the complexes of 1-(5-methyl-2-pyridyl)imidazolidine-2-thione (5h) and 1-(4-tert-butyl-2-pyridyl)imidazolidine-2-thione (5j) showed cytostatic effect against a whole panel of five human tumor cell lines. In conclusion, the only complexes that showed remarkably increased activity in comparison to the free ligands were those obtained from N-(2-pyridyl)imidazolidine-2-thiones 4c and 4e substituted with alkyl group at position 4 or 5 of pyridine ring.
authors.affiliation: Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdańsk, 80-416 Gdańsk, Poland. lbalewski@gumed.edu.pl.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Balewski
authors.affiliation: Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdańsk, 80-416 Gdańsk, Poland. saczew@gumed.edu.pl.
authors.forename: Franciszek
authors.initials: F
authors.lastname: Sączewski
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, University of Greifswald, L.-F.-Jahn Str., D-17489 Greifswald, Germany. bednarsk@uni-greifswald.de.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bednarski
authors.affiliation: Faculty of Chemistry, A. Mickiewicz University, 60-780 Poznań, Poland. magdan@amu.edu.pl.
authors.forename: Maria
authors.initials: M
authors.lastname: Gdaniec
authors.affiliation: Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdańsk, 80-416 Gdańsk, Poland. edziemidowicz-borys@dr-knoell-consult.com.
authors.forename: Ewa
authors.initials: E
authors.lastname: Borys
authors.affiliation: Department of Chemical Technology of Drugs, Faculty of Pharmacy, Medical University of Gdańsk, 80-416 Gdańsk, Poland. a.materna@gumed.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Makowska
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D013871:Thiones / Q000737:chemistry* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009942:Organometallic Compounds; D013871:Thiones; C000603235:dichloro(1-(4-tert-butyl-2-pyridyl)imidazolidine-2-thione)copper(II); D003300:Copper