[N,N′-Bis(salicylidene)-1,2-phenylenediamine]metal complexes with cell death promoting properties |
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Authors: | Annegret Hille Ingo Ott Ana Kitanovic Igor Kitanovic Hamed Alborzinia Elke Lederer Stefan Wölfl Nils Metzler-Nolte Sven Schäfer William S Sheldrick Caroline Bischof Ulrich Schatzschneider Ronald Gust |
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Institution: | 1. Institute of Pharmacy, Freie Universit?t Berlin, K?nigin-Luise-Strasse 2+4, 14195, Berlin, Germany 2. Institute of Pharmacy and Molecular Biotechnology, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany 3. Inorganic Chemistry I, Bioinorganic Chemistry, Faculty of Chemistry and Biochemistry, Ruhr-Universit?t Bochum, Universit?tsstrasse 150, 44801, Bochum, Germany 4. Analytical Chemistry, Faculty of Chemistry and Biochemistry, Ruhr-Universit?t Bochum, Universit?tsstrasse 150, 44801, Bochum, Germany
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Abstract: | We developed N,N′-bis(salicylidene)-1,2-phenylenediamine (salophene, 1) as a chelating agent for metal ions such as Mn(II/III), Fe(II/III), Co(II), Ni(II), Cu(II), and Zn(II). The resulting complexes,
from which owing to the carrier ligand a selective mode of action is assumed, were tested for antiproliferative effects on
the MCF-7 breast cancer cell line. The cytotoxicity in this assay depended on the nature of the transition metal used. Iron
complexes in oxidation states +II and +III (3, 4) strongly reduced cell proliferation in a concentration-dependent manner, whereas, e.g., the manganese analogues 5 and 6 were only marginally active. Therefore, the N,N′-bis(salicylidene)-1,2-phenylenediamine]iron(II/III) complexes 3 and 4 were selected for studies on the mode of action. Both complexes possessed high activity against various tumor cells, for
instance, MDA-MB-231 mammary carcinoma cells as well as HT-29 colon carcinoma cells. They were able to generate reactive oxygen
species, showed DNA binding, and induced apoptosis. Exchange of 1 by N,N′-bis(salicylidene)-1,2-cyclohexanediamine (saldach, 2) yielding complexes 7 and 8 reduced the in vitro effects drastically. An unequivocal mode of action cannot be deduced from these results, but it seems
to be very likely that cell death is caused by interference with more than one intracellular target.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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Keywords: | Antitumor activity Reactive oxygen species Salophene complexes DNA binding studies |
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