Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment
Over the past decade, metal complexes based on <i>N</i>-heterocyclic carbenes (NHCs) have attracted great attention due to their wide and exciting applications in material sciences and medicinal chemistry. In particular, the gold-based complexes are the focus of research efforts for the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/5/507 |
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| author | Jessica Ceramella Annaluisa Mariconda Marco Sirignano Domenico Iacopetta Camillo Rosano Alessia Catalano Carmela Saturnino Maria Stefania Sinicropi Pasquale Longo |
| author_facet | Jessica Ceramella Annaluisa Mariconda Marco Sirignano Domenico Iacopetta Camillo Rosano Alessia Catalano Carmela Saturnino Maria Stefania Sinicropi Pasquale Longo |
| author_sort | Jessica Ceramella |
| collection | DOAJ |
| description | Over the past decade, metal complexes based on <i>N</i>-heterocyclic carbenes (NHCs) have attracted great attention due to their wide and exciting applications in material sciences and medicinal chemistry. In particular, the gold-based complexes are the focus of research efforts for the development of new anticancer compounds. Literature data and recent results, obtained by our research group, reported the design, the synthesis and the good anticancer activity of some silver and gold complexes with NHC ligands. In particular, some of these complexes were active towards some breast cancer cell lines. Considering this evidence, here we report some new Au-NHC complexes prepared in order to improve solubility and biological activity. Among them, the compounds <b>1</b> and <b>6</b> showed an interesting anticancer activity towards the breast cancer MDA-MB-231 and MCF-7 cell lines, respectively. In addition, in vitro and in silico studies demonstrated that they were able to inhibit the activity of the human topoisomerases I and II and the actin polymerization reaction. Moreover, a downregulation of vimentin expression and a reduced translocation of NF-kB into the nucleus was observed. The interference with these vital cell structures induced breast cancer cells’ death by triggering the extrinsic apoptotic pathway. |
| first_indexed | 2024-03-10T03:10:38Z |
| format | Article |
| id | doaj.art-96632200e93f47dc87dbb98a4ab99b23 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T03:10:38Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-96632200e93f47dc87dbb98a4ab99b232023-11-23T12:33:38ZengMDPI AGPharmaceuticals1424-82472022-04-0115550710.3390/ph15050507Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer TreatmentJessica Ceramella0Annaluisa Mariconda1Marco Sirignano2Domenico Iacopetta3Camillo Rosano4Alessia Catalano5Carmela Saturnino6Maria Stefania Sinicropi7Pasquale Longo8Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Arcavacata di Rende, ItalyDepartment of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Chemistry and Biology, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Arcavacata di Rende, ItalyU.O. Proteomica e Spettrometria di Massa, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 1632 Genova, ItalyDepartment of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70126 Bari, ItalyDepartment of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Arcavacata di Rende, ItalyDepartment of Chemistry and Biology, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyOver the past decade, metal complexes based on <i>N</i>-heterocyclic carbenes (NHCs) have attracted great attention due to their wide and exciting applications in material sciences and medicinal chemistry. In particular, the gold-based complexes are the focus of research efforts for the development of new anticancer compounds. Literature data and recent results, obtained by our research group, reported the design, the synthesis and the good anticancer activity of some silver and gold complexes with NHC ligands. In particular, some of these complexes were active towards some breast cancer cell lines. Considering this evidence, here we report some new Au-NHC complexes prepared in order to improve solubility and biological activity. Among them, the compounds <b>1</b> and <b>6</b> showed an interesting anticancer activity towards the breast cancer MDA-MB-231 and MCF-7 cell lines, respectively. In addition, in vitro and in silico studies demonstrated that they were able to inhibit the activity of the human topoisomerases I and II and the actin polymerization reaction. Moreover, a downregulation of vimentin expression and a reduced translocation of NF-kB into the nucleus was observed. The interference with these vital cell structures induced breast cancer cells’ death by triggering the extrinsic apoptotic pathway.https://www.mdpi.com/1424-8247/15/5/507<i>N</i>-heterocyclic carbeneshuman topoisomerasesactindocking studiesbreast cancer cellsmulti-target agents |
| spellingShingle | Jessica Ceramella Annaluisa Mariconda Marco Sirignano Domenico Iacopetta Camillo Rosano Alessia Catalano Carmela Saturnino Maria Stefania Sinicropi Pasquale Longo Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment Pharmaceuticals <i>N</i>-heterocyclic carbenes human topoisomerases actin docking studies breast cancer cells multi-target agents |
| title | Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment |
| title_full | Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment |
| title_fullStr | Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment |
| title_full_unstemmed | Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment |
| title_short | Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment |
| title_sort | novel au carbene complexes as promising multi target agents in breast cancer treatment |
| topic | <i>N</i>-heterocyclic carbenes human topoisomerases actin docking studies breast cancer cells multi-target agents |
| url | https://www.mdpi.com/1424-8247/15/5/507 |
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