Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal
An important challenge in the field of anticancer chemotherapy is the search for new species to overcome the resistance of standard drugs. An interesting approach is to link bioactive ligands to metal fragments. In this work, we have synthesized a set of <i>p</i>-cymene-Ru or cyclopentad...
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MDPI AG
2021-09-01
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| Seria: | Pharmaceutics |
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| Dostęp online: | https://www.mdpi.com/1999-4923/13/10/1540 |
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| author | Ana R. Rubio Rocío González Natalia Busto Mónica Vaquero Ana L. Iglesias Félix A. Jalón Gustavo Espino Ana M. Rodríguez Begoña García Blanca R. Manzano |
| author_facet | Ana R. Rubio Rocío González Natalia Busto Mónica Vaquero Ana L. Iglesias Félix A. Jalón Gustavo Espino Ana M. Rodríguez Begoña García Blanca R. Manzano |
| author_sort | Ana R. Rubio |
| collection | DOAJ |
| description | An important challenge in the field of anticancer chemotherapy is the search for new species to overcome the resistance of standard drugs. An interesting approach is to link bioactive ligands to metal fragments. In this work, we have synthesized a set of <i>p</i>-cymene-Ru or cyclopentadienyl-M (M = Rh, Ir) complexes with four chrysin-derived pro-ligands with different -OR substituents at position 7 of ring A. The introduction of a piperidine ring on chrysin led to the highly cytotoxic pro-ligand <b>HL4</b> and its metal complexes <b>L4-M</b> (SW480 and A549 cell lines, cytotoxic order: <b>L4-Ir</b> > <b>L4-Ru</b> ≈ <b>L4-Rh</b>). <b>HL4</b> and its complexes induce apoptosis and can overcome cis-platinum resistance. However, <b>HL4</b> turns out to be more cytotoxic in healthy than in tumor cells in contrast to its metal complexes which displayed higher selectivity than cisplatin towards cancer cells. All <b>L4-M</b> complexes interact with double stranded DNA. Nonetheless, the influence of the metal is clear because only complex <b>L4-Ir</b> causes DNA cleavage, through the generation of highly reactive oxygen species (<sup>1</sup>O<sub>2</sub>). This result supports the hypothesis of a potential dual mechanism consisting of two different chemical pathways: DNA binding and ROS generation. This behavior provides this complex with a great effectivity in terms of cytotoxicity. |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T06:17:20Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8aca9a93f84c4c7da1fdcadd21387fe92023-11-22T19:37:13ZengMDPI AGPharmaceutics1999-49232021-09-011310154010.3390/pharmaceutics13101540Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the MetalAna R. Rubio0Rocío González1Natalia Busto2Mónica Vaquero3Ana L. Iglesias4Félix A. Jalón5Gustavo Espino6Ana M. Rodríguez7Begoña García8Blanca R. Manzano9Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, SpainFacultad de Ciencias y Tecnologías Químicas-IRICA, Universidad de Castilla-La Mancha, Avda. C. J. Cela 10, 13071 Ciudad Real, SpainDepartamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, SpainDepartamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, SpainFacultad de Ciencias y Tecnologías Químicas-IRICA, Universidad de Castilla-La Mancha, Avda. C. J. Cela 10, 13071 Ciudad Real, SpainFacultad de Ciencias y Tecnologías Químicas-IRICA, Universidad de Castilla-La Mancha, Avda. C. J. Cela 10, 13071 Ciudad Real, SpainDepartamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, SpainDepartamento de Química Inorgánica, Orgánica y Bioquímica, Escuela Técnica Superior de Ingenieros Industriales, Universidad de Castilla-La Mancha, Avda. C. J. Cela 2, 13071 Ciudad Real, SpainDepartamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, SpainFacultad de Ciencias y Tecnologías Químicas-IRICA, Universidad de Castilla-La Mancha, Avda. C. J. Cela 10, 13071 Ciudad Real, SpainAn important challenge in the field of anticancer chemotherapy is the search for new species to overcome the resistance of standard drugs. An interesting approach is to link bioactive ligands to metal fragments. In this work, we have synthesized a set of <i>p</i>-cymene-Ru or cyclopentadienyl-M (M = Rh, Ir) complexes with four chrysin-derived pro-ligands with different -OR substituents at position 7 of ring A. The introduction of a piperidine ring on chrysin led to the highly cytotoxic pro-ligand <b>HL4</b> and its metal complexes <b>L4-M</b> (SW480 and A549 cell lines, cytotoxic order: <b>L4-Ir</b> > <b>L4-Ru</b> ≈ <b>L4-Rh</b>). <b>HL4</b> and its complexes induce apoptosis and can overcome cis-platinum resistance. However, <b>HL4</b> turns out to be more cytotoxic in healthy than in tumor cells in contrast to its metal complexes which displayed higher selectivity than cisplatin towards cancer cells. All <b>L4-M</b> complexes interact with double stranded DNA. Nonetheless, the influence of the metal is clear because only complex <b>L4-Ir</b> causes DNA cleavage, through the generation of highly reactive oxygen species (<sup>1</sup>O<sub>2</sub>). This result supports the hypothesis of a potential dual mechanism consisting of two different chemical pathways: DNA binding and ROS generation. This behavior provides this complex with a great effectivity in terms of cytotoxicity.https://www.mdpi.com/1999-4923/13/10/1540chrysin ligandsiridiumrutheniumrhodiumcancermetallodrugs |
| spellingShingle | Ana R. Rubio Rocío González Natalia Busto Mónica Vaquero Ana L. Iglesias Félix A. Jalón Gustavo Espino Ana M. Rodríguez Begoña García Blanca R. Manzano Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal Pharmaceutics chrysin ligands iridium ruthenium rhodium cancer metallodrugs |
| title | Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal |
| title_full | Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal |
| title_fullStr | Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal |
| title_full_unstemmed | Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal |
| title_short | Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal |
| title_sort | anticancer activity of half sandwich ru rh and ir complexes with chrysin derived ligands strong effect of the side chain in the ligand and influence of the metal |
| topic | chrysin ligands iridium ruthenium rhodium cancer metallodrugs |
| url | https://www.mdpi.com/1999-4923/13/10/1540 |
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