Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative

<b>Background:</b> Carbazoles represent one of the most important classes of nitrogen-based tricyclic aromatic heterocycles and are present in natural sources and chemically obtained drugs. Recently, several research groups disclosed their large biological and chemical applications in di...

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Main Authors: Jessica Ceramella, Camillo Rosano, Domenico Iacopetta, Iméne Ben Toumia, Leila Chekir-Ghedira, Mouna Maatouk, Annaluisa Mariconda, Pasquale Longo, Patrick Dallemagne, Christophe Rochais, Maria Stefania Sinicropi
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Language:English
Published: MDPI AG 2025-03-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/4/415
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author Jessica Ceramella
Camillo Rosano
Domenico Iacopetta
Iméne Ben Toumia
Leila Chekir-Ghedira
Mouna Maatouk
Annaluisa Mariconda
Pasquale Longo
Patrick Dallemagne
Christophe Rochais
Maria Stefania Sinicropi
author_facet Jessica Ceramella
Camillo Rosano
Domenico Iacopetta
Iméne Ben Toumia
Leila Chekir-Ghedira
Mouna Maatouk
Annaluisa Mariconda
Pasquale Longo
Patrick Dallemagne
Christophe Rochais
Maria Stefania Sinicropi
author_sort Jessica Ceramella
collection DOAJ
description <b>Background:</b> Carbazoles represent one of the most important classes of nitrogen-based tricyclic aromatic heterocycles and are present in natural sources and chemically obtained drugs. Recently, several research groups disclosed their large biological and chemical applications in different fields, leading to an increased interest towards this class of molecules. Some of the obtained derivatives have been successfully employed in the clinical treatment of different tumor types, but the onset of heavy side effects impaired their efficacy and discouraged their use. Pursuing the aim of obtaining carbazoles with less negative features, a lot of chemically modified compounds have been produced and evaluated. <b>Objectives/Methods</b>: In this paper, we describe the in vitro and in vivo evaluation of a bis-carbazole derivative with strong anticancer properties against two breast cancer cell lines. <b>Results</b>: This compound has been found to impact the cell cytoskeleton dynamics, triggering the activation of some key proteins playing a role in the intrinsic and extrinsic apoptotic pathways. Equally important, this derivative has been found to be selective for cancer cells and has shown a safe profile in Balb/c-treated mice. <b>Conclusions</b>: Overall, the disclosed outcomes represent an important landmark for encouraging further studies directed toward the potentiation of this lead to be potentially exploited in both preclinical and clinical applications.
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spelling doaj-art-bf852d5dc901412ca99ed5a48e5b7b5f2025-08-20T03:13:32ZengMDPI AGPharmaceutics1999-49232025-03-0117441510.3390/pharmaceutics17040415Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole DerivativeJessica Ceramella0Camillo Rosano1Domenico Iacopetta2Iméne Ben Toumia3Leila Chekir-Ghedira4Mouna Maatouk5Annaluisa Mariconda6Pasquale Longo7Patrick Dallemagne8Christophe Rochais9Maria Stefania Sinicropi10Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, 87036 Arcavacata di Rende, ItalyU.O. Proteomica e Spettrometria di Massa, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, 16132 Genova, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, 87036 Arcavacata di Rende, ItalyU.O. Proteomica e Spettrometria di Massa, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, 16132 Genova, ItalyLaboratory of Bioactive Natural Substances and Biotechnology, Faculty of Dentistry of Monastir, University of Monastir, Monastir 5000, TunisiaLaboratory of Bioactive Natural Substances and Biotechnology, Faculty of Dentistry of Monastir, University of Monastir, Monastir 5000, TunisiaDepartment of Basic and Applied Sciences, University of Basilicata, Via dell’Ateneo Lucano, 10, 85100 Potenza, ItalyDepartment of Chemistry and Biology “A. Zambelli”, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyUniversité Caen Normandie, Normandie University, CERMN UR4258, F-14000 Caen, FranceUniversité Caen Normandie, Normandie University, CERMN UR4258, F-14000 Caen, FranceDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, 87036 Arcavacata di Rende, Italy<b>Background:</b> Carbazoles represent one of the most important classes of nitrogen-based tricyclic aromatic heterocycles and are present in natural sources and chemically obtained drugs. Recently, several research groups disclosed their large biological and chemical applications in different fields, leading to an increased interest towards this class of molecules. Some of the obtained derivatives have been successfully employed in the clinical treatment of different tumor types, but the onset of heavy side effects impaired their efficacy and discouraged their use. Pursuing the aim of obtaining carbazoles with less negative features, a lot of chemically modified compounds have been produced and evaluated. <b>Objectives/Methods</b>: In this paper, we describe the in vitro and in vivo evaluation of a bis-carbazole derivative with strong anticancer properties against two breast cancer cell lines. <b>Results</b>: This compound has been found to impact the cell cytoskeleton dynamics, triggering the activation of some key proteins playing a role in the intrinsic and extrinsic apoptotic pathways. Equally important, this derivative has been found to be selective for cancer cells and has shown a safe profile in Balb/c-treated mice. <b>Conclusions</b>: Overall, the disclosed outcomes represent an important landmark for encouraging further studies directed toward the potentiation of this lead to be potentially exploited in both preclinical and clinical applications.https://www.mdpi.com/1999-4923/17/4/415carbazole derivativesanticancercytoskeletonapoptosistoxicity studies
spellingShingle Jessica Ceramella
Camillo Rosano
Domenico Iacopetta
Iméne Ben Toumia
Leila Chekir-Ghedira
Mouna Maatouk
Annaluisa Mariconda
Pasquale Longo
Patrick Dallemagne
Christophe Rochais
Maria Stefania Sinicropi
Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative
Pharmaceutics
carbazole derivatives
anticancer
cytoskeleton
apoptosis
toxicity studies
title Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative
title_full Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative
title_fullStr Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative
title_full_unstemmed Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative
title_short Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative
title_sort anti breast cancer properties and in vivo safety profile of a bis carbazole derivative
topic carbazole derivatives
anticancer
cytoskeleton
apoptosis
toxicity studies
url https://www.mdpi.com/1999-4923/17/4/415
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