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N‐Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin

In recent years, the number of people suffering from cancer has risen rapidly and the World Health Organization and U.S. and European governments have identified this pathology as a priority issue. It is known that most bioactive anticancer molecules do not target a single protein but exert pleiotro...

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Autores principales: Mariconda, Annaluisa, Iacopetta, Domenico, Sirignano, Marco, Ceramella, Jessica, Costabile, Chiara, Pellegrino, Michele, Rosano, Camillo, Catalano, Alessia, Saturnino, Carmela, El‐Kashef, Hussein, Aquaro, Stefano, Sinicropi, Maria Stefania, Longo, Pasquale
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9804882/
https://www.ncbi.nlm.nih.gov/pubmed/35904129
http://dx.doi.org/10.1002/cmdc.202200345
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author Mariconda, Annaluisa
Iacopetta, Domenico
Sirignano, Marco
Ceramella, Jessica
Costabile, Chiara
Pellegrino, Michele
Rosano, Camillo
Catalano, Alessia
Saturnino, Carmela
El‐Kashef, Hussein
Aquaro, Stefano
Sinicropi, Maria Stefania
Longo, Pasquale
author_facet Mariconda, Annaluisa
Iacopetta, Domenico
Sirignano, Marco
Ceramella, Jessica
Costabile, Chiara
Pellegrino, Michele
Rosano, Camillo
Catalano, Alessia
Saturnino, Carmela
El‐Kashef, Hussein
Aquaro, Stefano
Sinicropi, Maria Stefania
Longo, Pasquale
author_sort Mariconda, Annaluisa
collection PubMed
description In recent years, the number of people suffering from cancer has risen rapidly and the World Health Organization and U.S. and European governments have identified this pathology as a priority issue. It is known that most bioactive anticancer molecules do not target a single protein but exert pleiotropic effects, simultaneously affecting multiple pathways. In our study, we designed and synthesized a new series of silver N‐heterocyclic carbene (NHC) complexes [(NHC)(2)Ag](+)[AgX(2)](−) (X=iodide or acetate). The new complexes were active against two human breast cancer cell lines, MCF‐7 and MDA‐MB‐231. These compounds showed multiple target actions as anticancer, by inhibiting in vitro the activity of the human topoisomerases I and II and interfering with the cytoskeleton dynamic, as also confirmed by in silico studies. Moreover, the antimicrobial activity of these silver complexes was studied against Gram‐positive/negative bacteria. These dual properties provide a two‐tiered approach, making these compounds of interest to be further deepened for the development of new chemotherapeutic agents.
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spelling pubmed-98048822023-01-06 N‐Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin Mariconda, Annaluisa Iacopetta, Domenico Sirignano, Marco Ceramella, Jessica Costabile, Chiara Pellegrino, Michele Rosano, Camillo Catalano, Alessia Saturnino, Carmela El‐Kashef, Hussein Aquaro, Stefano Sinicropi, Maria Stefania Longo, Pasquale ChemMedChem Research Articles In recent years, the number of people suffering from cancer has risen rapidly and the World Health Organization and U.S. and European governments have identified this pathology as a priority issue. It is known that most bioactive anticancer molecules do not target a single protein but exert pleiotropic effects, simultaneously affecting multiple pathways. In our study, we designed and synthesized a new series of silver N‐heterocyclic carbene (NHC) complexes [(NHC)(2)Ag](+)[AgX(2)](−) (X=iodide or acetate). The new complexes were active against two human breast cancer cell lines, MCF‐7 and MDA‐MB‐231. These compounds showed multiple target actions as anticancer, by inhibiting in vitro the activity of the human topoisomerases I and II and interfering with the cytoskeleton dynamic, as also confirmed by in silico studies. Moreover, the antimicrobial activity of these silver complexes was studied against Gram‐positive/negative bacteria. These dual properties provide a two‐tiered approach, making these compounds of interest to be further deepened for the development of new chemotherapeutic agents. John Wiley and Sons Inc. 2022-08-17 2022-09-16 /pmc/articles/PMC9804882/ /pubmed/35904129 http://dx.doi.org/10.1002/cmdc.202200345 Text en © 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Mariconda, Annaluisa
Iacopetta, Domenico
Sirignano, Marco
Ceramella, Jessica
Costabile, Chiara
Pellegrino, Michele
Rosano, Camillo
Catalano, Alessia
Saturnino, Carmela
El‐Kashef, Hussein
Aquaro, Stefano
Sinicropi, Maria Stefania
Longo, Pasquale
N‐Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin
title N‐Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin
title_full N‐Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin
title_fullStr N‐Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin
title_full_unstemmed N‐Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin
title_short N‐Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin
title_sort n‐heterocyclic carbene (nhc) silver complexes as versatile chemotherapeutic agents targeting human topoisomerases and actin
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9804882/
https://www.ncbi.nlm.nih.gov/pubmed/35904129
http://dx.doi.org/10.1002/cmdc.202200345
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