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Dinuclear doubly bridged phenoxido copper(II) complexes as efficient anticancer agents.
Massoud, Salah S; Louka, Febee R; Salem, Nahed M H; Fischer, Roland C; Torvisco, Ana; Mautner, Franz A; Vanco, Ján; Belza, Jan; Dvorák, Zdenek; Trávnícek, Zdenek.
Afiliação
  • Massoud SS; Department of Chemistry, University of Louisiana at Lafayette, P.O. Box 43700, Lafayette, LA, 70504, USA; Department of Chemistry, Faculty of Science, Alexandria University, Moharam Bey, 21511, Alexandria, Egypt. Electronic address: ssmassoud@louisiana.edu.
  • Louka FR; Department of Chemistry, University of Louisiana at Lafayette, P.O. Box 43700, Lafayette, LA, 70504, USA.
  • Salem NMH; Department of Chemistry, Faculty of Science, Alexandria University, Moharam Bey, 21511, Alexandria, Egypt.
  • Fischer RC; Institut für Anorganische Chemische, Technische Universität Graz, Stremayrgasse 9/V, A-8010, Graz, Austria.
  • Torvisco A; Institut für Anorganische Chemische, Technische Universität Graz, Stremayrgasse 9/V, A-8010, Graz, Austria.
  • Mautner FA; Institut für Physikalische and Theoretische Chemie, Technische Universität Graz, Stremayrgasse 9/II, A-8010, Graz, Austria. Electronic address: mautner@tugraz.at.
  • Vanco J; Czech Advanced Technology and Research Institute, Regional Centre of Advanced Technologies and Materials, Palacký University, Krízkovského 511/8, CZ-779 00, Olomouc, Czech Republic.
  • Belza J; Czech Advanced Technology and Research Institute, Regional Centre of Advanced Technologies and Materials, Palacký University, Krízkovského 511/8, CZ-779 00, Olomouc, Czech Republic.
  • Dvorák Z; Department of Cell Biology and Genetics, Faculty of Science, Palacký University, Slechtitelu 27, CZ-783 71, Olomouc, Czech Republic.
  • Trávnícek Z; Czech Advanced Technology and Research Institute, Regional Centre of Advanced Technologies and Materials, Palacký University, Krízkovského 511/8, CZ-779 00, Olomouc, Czech Republic. Electronic address: zdenek.travnicek@upol.cz.
Eur J Med Chem ; 246: 114992, 2023 Jan 15.
Article em En | MEDLINE | ID: mdl-36525695
ABSTRACT
Two cationic [Cu2(L1-2)2](ClO4)2 (1, 2), and four neutral doubly bridged-phenoxido-copper(II) complexes [Cu2(L3-4)2] (3, 4) and [Cu2(L5-6)2(H2O)]‧2H2O (5, 6) as well as 1D polymeric catena-[Cu(L7)] (7), where HL1-2 and H2L3-7 represent tripodal tetradentate pyridyl or aliphatic-amino groups based 2,4-disubstituted phenolates, were synthesized and thoroughly characterized by various spectroscopic methods and single crystal X-ray analysis. The molecular structures of the complexes exhibited diverse geometrical environments around the central Cu(II) atoms. The in vitro antiproliferative activity of the isolated complexes and selected parent free ligands were screened against some human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, MCF-7). The most promising cytotoxicity against cancer cells were obtained for 1-6, while complex 6 was found as the best performing as compared to the reference drug cisplatin. The cytotoxicity study of complex 6 was therefore extended to wider variety of cancer cell lines (HOS, A549, PANC-1, CaCo2, HeLa) and results revealed its significant cytotoxicity on all investigated human cancer cells. The cell uptake study showed that cytotoxicity of 6 (3 µM concentration and 24 h of incubation) against A2780 cells was almost independent from the intracellular levels of copper. The effect of complexes 4, 6 and 7 on cell cycle of A2780 cells indicates that the mechanism of action in these complexes is not only different from that of cisplatin but also different among them. Complex 7 was able to induce apoptosis in A2780 cells, while complexes 4 and 6 did not and on the other hand, they showed considerable effect on autophagy induction and there are some clues that these complexes were able to induce cuproptosis in A2780 cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Complexos de Coordenação / Antineoplásicos Limite: Female / Humans Idioma: En Revista: Eur J Med Chem Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Complexos de Coordenação / Antineoplásicos Limite: Female / Humans Idioma: En Revista: Eur J Med Chem Ano de publicação: 2023 Tipo de documento: Article