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Abstract
The oncological use of cisplatin is hindered by its severe side eects and a very important resistance problem. To overcome these problems, scientists have attempted to design new generation transition-metal anticancer complexes. In this study, we present new complexes, ruthenium(II) [(6-p-cymene)RuCl(py2CO)]PF6 (1), iridium(III) [(5-Cp)IrCl(py2CO)]PF6 (2), and NH4[IrCl4(py2CO)]H2O (3), based on di-2-pyridylketone (py2CO). The prepared complexes were characterized by FTIR, 1H, 13C, 15N NMR, UV-Vis, PL and elemental analysis techniques. The single-crystal X-ray structure analysis and comparative data revealed pseudo-octahedral half-sandwich 1 and 2 complexes and octahedral tetrachloroiridate(III) 3 with a rare chelating 2N,O coordination mode of py2CO. The compounds were tested in vitro against three cancer cell lines—colorectal adenoma (LoVo), myelomonocytic leukaemia (MV-4-11), breast adenocarcinoma (MCF-7), and normal fibroblasts (BALB/3T3). The most promising results were obtained for iridium(III) complex 3 against MV-4-11 (IC50 = 35.8 13.9 g/mL) without a toxic eect against normal BALB/3T3, which pointed towards its selectivity as a potential anticancer agent. Extensive research into their mode of binding with DNA confirmed for 1 and 2 complexes non-classical binding modes, while the 3D circular dichroism (CD) experiment (DTm) suggested that 3 induced the probable formation of covalent bonds with DNA. In addition, the obtained iridium complexes induce ROS, which, in synergy with hydrolysis promoting DNA bonding, may lead to cancer cell death.
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Authors (9)
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Joanna Masternak dr hab.
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Agnieszka Gilewska
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Barbara Barszcz
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Iwona Łakomska
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Jerzy Sitkowski
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Joanna Wietrzyk
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Anna Kamecka
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Magdalena Milczarek
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Full text
- Publication version
- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ma13163491
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- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
-
Materials
no. 13,
ISSN: 1996-1944 - Language:
- English
- Publication year:
- 2020
- Bibliographic description:
- Masternak J., Gilewska A., Barszcz B., Łakomska I., Kazimierczuk K., Sitkowski J., Wietrzyk J., Kamecka A., Milczarek M.: Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents// Materials -Vol. 13,iss. 16 (2020), s.3491-
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ma13163491
- Verified by:
- Gdańsk University of Technology
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