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Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells

[Image: see text] Herein, we report a series of new octahedral iridium(III) complexes Ir1–Ir9 of the type [Ir(N^N^N)(C^N)Cl]PF(6) (N^N^N = 4′-(p-tolyl)-2,2′:6′,2″-terpyridine; C^N = deprotonated 2-arylbenzimidazole backbone) to introduce new metal-based compounds for effective inhibition of metastat...

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Autores principales: Novohradsky, Vojtech, Marco, Alicia, Markova, Lenka, Cutillas, Natalia, Ruiz, José, Brabec, Viktor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388354/
https://www.ncbi.nlm.nih.gov/pubmed/37410386
http://dx.doi.org/10.1021/acs.jmedchem.3c00586
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author Novohradsky, Vojtech
Marco, Alicia
Markova, Lenka
Cutillas, Natalia
Ruiz, José
Brabec, Viktor
author_facet Novohradsky, Vojtech
Marco, Alicia
Markova, Lenka
Cutillas, Natalia
Ruiz, José
Brabec, Viktor
author_sort Novohradsky, Vojtech
collection PubMed
description [Image: see text] Herein, we report a series of new octahedral iridium(III) complexes Ir1–Ir9 of the type [Ir(N^N^N)(C^N)Cl]PF(6) (N^N^N = 4′-(p-tolyl)-2,2′:6′,2″-terpyridine; C^N = deprotonated 2-arylbenzimidazole backbone) to introduce new metal-based compounds for effective inhibition of metastatic processes in triple-negative breast cancer (TNBC). The results show that the structural modifications within the C^N scaffold strongly impact the antimetastatic properties of these complexes in TNBC cells. Furthermore, testing the antimetastatic effects of the investigated Ir complexes revealed that the highest antimetastatic activity in TNBC cells is exhibited by complex Ir1. This result was in contrast to the effects of the clinically used drug doxorubicin used in conventional chemotherapy of TNBC, which conversely promoted metastatic properties of TNBC cells. Thus, the latter result suggests that doxorubicin chemotherapy may increase the risk of metastasis of breast cancer cells, so the search for new drugs to treat breast cancer that would show better antitumor effects than doxorubicin is justified.
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spelling pubmed-103883542023-08-01 Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells Novohradsky, Vojtech Marco, Alicia Markova, Lenka Cutillas, Natalia Ruiz, José Brabec, Viktor J Med Chem [Image: see text] Herein, we report a series of new octahedral iridium(III) complexes Ir1–Ir9 of the type [Ir(N^N^N)(C^N)Cl]PF(6) (N^N^N = 4′-(p-tolyl)-2,2′:6′,2″-terpyridine; C^N = deprotonated 2-arylbenzimidazole backbone) to introduce new metal-based compounds for effective inhibition of metastatic processes in triple-negative breast cancer (TNBC). The results show that the structural modifications within the C^N scaffold strongly impact the antimetastatic properties of these complexes in TNBC cells. Furthermore, testing the antimetastatic effects of the investigated Ir complexes revealed that the highest antimetastatic activity in TNBC cells is exhibited by complex Ir1. This result was in contrast to the effects of the clinically used drug doxorubicin used in conventional chemotherapy of TNBC, which conversely promoted metastatic properties of TNBC cells. Thus, the latter result suggests that doxorubicin chemotherapy may increase the risk of metastasis of breast cancer cells, so the search for new drugs to treat breast cancer that would show better antitumor effects than doxorubicin is justified. American Chemical Society 2023-07-06 /pmc/articles/PMC10388354/ /pubmed/37410386 http://dx.doi.org/10.1021/acs.jmedchem.3c00586 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Novohradsky, Vojtech
Marco, Alicia
Markova, Lenka
Cutillas, Natalia
Ruiz, José
Brabec, Viktor
Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells
title Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells
title_full Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells
title_fullStr Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells
title_full_unstemmed Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells
title_short Ir(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells
title_sort ir(iii) compounds containing a terdentate ligand are potent inhibitors of proliferation and effective antimetastatic agents in aggressive triple-negative breast cancer cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388354/
https://www.ncbi.nlm.nih.gov/pubmed/37410386
http://dx.doi.org/10.1021/acs.jmedchem.3c00586
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