Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents
The oncological use of cisplatin is hindered by its severe side effects 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) [(η<sup>...
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doaj-f57e69c0335441dbac66bae9e4560be52020-11-25T02:54:54ZengMDPI AGMaterials1996-19442020-08-01133491349110.3390/ma13163491Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer AgentsJoanna Masternak0Agnieszka Gilewska1Iwona Łakomska2Barbara Barszcz3Katarzyna Kazimierczuk4Jerzy Sitkowski5Joanna Wietrzyk6Anna Kamecka7Magdalena Milczarek8Institute of Chemistry, Jan Kochanowski University, Uniwersytecka 7, 25-406 Kielce, PolandInstitute of Chemistry, Jan Kochanowski University, Uniwersytecka 7, 25-406 Kielce, PolandFaculty of Chemistry, Nicolaus Copernicus University in Toruń, Gagarina 7, 87-100 Toruń, PolandInstitute of Chemistry, Jan Kochanowski University, Uniwersytecka 7, 25-406 Kielce, PolandDepartment of Inorganic Chemistry, Faculty of Chemistry, Gdańsk University of Technology, Narutowicza 11/12 G., 80-233 Gdańsk, PolandInstitute of Organic Chemistry, Polish Academic of Science, Kasprzaka 44/52, 01-224 Warszawa, PolandHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wrocław, PolandInstitute of Chemistry, Faculty of Sciences, University of Natural Sciences and Humanities in Siedlce, 3 Maja 54, 08-110 Siedlce, PolandHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wrocław, PolandThe oncological use of cisplatin is hindered by its severe side effects 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) [(η<sup>6</sup>-<i>p</i>-cymene)RuCl(py<sub>2</sub>CO)]PF<sub>6</sub> (<b>1</b>), iridium(III) [(η<sup>5</sup>-Cp)IrCl(py<sub>2</sub>CO)]PF<sub>6</sub> (<b>2</b>), and NH<sub>4</sub>[IrCl<sub>4</sub>(py<sub>2</sub>CO)]·H<sub>2</sub>O (<b>3</b>), based on di-2-pyridylketone (py<sub>2</sub>CO). The prepared complexes were characterized by FTIR, <sup>1</sup>H, <sup>13</sup>C, <sup>15</sup>N NMR, UV-Vis, PL and elemental analysis techniques. The single-crystal X-ray structure analysis and comparative data revealed pseudo-octahedral half-sandwich <b>1</b> and <b>2</b> complexes and octahedral tetrachloroiridate(III) <b>3</b> with a rare chelating κ<sup>2</sup>N,O coordination mode of py<sub>2</sub>CO. The compounds were tested <i>in vitro</i> 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 <b>3</b> against MV-4-11 (IC<sub>50</sub> = 35.8 ± 13.9 µg/mL) without a toxic effect 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 <b>1</b> and <b>2</b> complexes non-classical binding modes, while the 3D circular dichroism (CD) experiment (ΔT<sub>m</sub>) suggested that <b>3</b> 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.https://www.mdpi.com/1996-1944/13/16/3491iridium(III) complexesruthenium half-sandwichcytotoxicityDNA interactions |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Joanna Masternak Agnieszka Gilewska Iwona Łakomska Barbara Barszcz Katarzyna Kazimierczuk Jerzy Sitkowski Joanna Wietrzyk Anna Kamecka Magdalena Milczarek |
| spellingShingle |
Joanna Masternak Agnieszka Gilewska Iwona Łakomska Barbara Barszcz Katarzyna Kazimierczuk Jerzy Sitkowski Joanna Wietrzyk Anna Kamecka Magdalena Milczarek Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents Materials iridium(III) complexes ruthenium half-sandwich cytotoxicity DNA interactions |
| author_facet |
Joanna Masternak Agnieszka Gilewska Iwona Łakomska Barbara Barszcz Katarzyna Kazimierczuk Jerzy Sitkowski Joanna Wietrzyk Anna Kamecka Magdalena Milczarek |
| author_sort |
Joanna Masternak |
| title |
Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents |
| title_short |
Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents |
| title_full |
Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents |
| title_fullStr |
Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents |
| title_full_unstemmed |
Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents |
| title_sort |
ruthenium(ii) and iridium(iii) complexes as tested materials for new anticancer agents |
| publisher |
MDPI AG |
| series |
Materials |
| issn |
1996-1944 |
| publishDate |
2020-08-01 |
| description |
The oncological use of cisplatin is hindered by its severe side effects 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) [(η<sup>6</sup>-<i>p</i>-cymene)RuCl(py<sub>2</sub>CO)]PF<sub>6</sub> (<b>1</b>), iridium(III) [(η<sup>5</sup>-Cp)IrCl(py<sub>2</sub>CO)]PF<sub>6</sub> (<b>2</b>), and NH<sub>4</sub>[IrCl<sub>4</sub>(py<sub>2</sub>CO)]·H<sub>2</sub>O (<b>3</b>), based on di-2-pyridylketone (py<sub>2</sub>CO). The prepared complexes were characterized by FTIR, <sup>1</sup>H, <sup>13</sup>C, <sup>15</sup>N NMR, UV-Vis, PL and elemental analysis techniques. The single-crystal X-ray structure analysis and comparative data revealed pseudo-octahedral half-sandwich <b>1</b> and <b>2</b> complexes and octahedral tetrachloroiridate(III) <b>3</b> with a rare chelating κ<sup>2</sup>N,O coordination mode of py<sub>2</sub>CO. The compounds were tested <i>in vitro</i> 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 <b>3</b> against MV-4-11 (IC<sub>50</sub> = 35.8 ± 13.9 µg/mL) without a toxic effect 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 <b>1</b> and <b>2</b> complexes non-classical binding modes, while the 3D circular dichroism (CD) experiment (ΔT<sub>m</sub>) suggested that <b>3</b> 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. |
| topic |
iridium(III) complexes ruthenium half-sandwich cytotoxicity DNA interactions |
| url |
https://www.mdpi.com/1996-1944/13/16/3491 |
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