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Synthesis of Curcumin Derivatives and Analysis of Their Antitumor Effects in Triple Negative Breast Cancer (TNBC) Cell Lines

We analyzed antitumor effects of a series of curcumin analogues. Some of them were obtained by reaction of substitution involving the two phenolic OH groups of curcumin while the analogues with a substituent at C-4 was prepared following an original procedure that regards the condensation of benzene...

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Autores principales: Bonaccorsi, Paola Maria, Labbozzetta, Manuela, Barattucci, Anna, Salerno, Tania Maria Grazia, Poma, Paola, Notarbartolo, Monica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958375/
https://www.ncbi.nlm.nih.gov/pubmed/31717764
http://dx.doi.org/10.3390/ph12040161
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author Bonaccorsi, Paola Maria
Labbozzetta, Manuela
Barattucci, Anna
Salerno, Tania Maria Grazia
Poma, Paola
Notarbartolo, Monica
author_facet Bonaccorsi, Paola Maria
Labbozzetta, Manuela
Barattucci, Anna
Salerno, Tania Maria Grazia
Poma, Paola
Notarbartolo, Monica
author_sort Bonaccorsi, Paola Maria
collection PubMed
description We analyzed antitumor effects of a series of curcumin analogues. Some of them were obtained by reaction of substitution involving the two phenolic OH groups of curcumin while the analogues with a substituent at C-4 was prepared following an original procedure that regards the condensation of benzenesulfenic acid onto the nucleophilic central carbon of the curcumin skeleton. We analyzed cytotoxic effects of such derivatives on two TNBC (triple negative breast cancer) cell lines, SUM 149 and MDA-MB-231, but only three of them showed an IC(50) in a lower micromolar range with respect to curcumin. We also focused on these three derivatives that in both cell lines exhibited a higher or at least equivalent pro-apoptotic effect than curcumin. The analysis of molecular mechanisms of action of the curcumin derivatives under study has highlighted that they decreased NF-κB transcriptional factor activity, and consequently the expression of some NF-κB targets. Our data confirmed once again that curcumin may represent a very good lead compound to design analogues with higher antitumor capacities and able to overcome drug resistance with respect to conventional ones, even in tumors difficult to treat as TNBC.
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spelling pubmed-69583752020-01-23 Synthesis of Curcumin Derivatives and Analysis of Their Antitumor Effects in Triple Negative Breast Cancer (TNBC) Cell Lines Bonaccorsi, Paola Maria Labbozzetta, Manuela Barattucci, Anna Salerno, Tania Maria Grazia Poma, Paola Notarbartolo, Monica Pharmaceuticals (Basel) Communication We analyzed antitumor effects of a series of curcumin analogues. Some of them were obtained by reaction of substitution involving the two phenolic OH groups of curcumin while the analogues with a substituent at C-4 was prepared following an original procedure that regards the condensation of benzenesulfenic acid onto the nucleophilic central carbon of the curcumin skeleton. We analyzed cytotoxic effects of such derivatives on two TNBC (triple negative breast cancer) cell lines, SUM 149 and MDA-MB-231, but only three of them showed an IC(50) in a lower micromolar range with respect to curcumin. We also focused on these three derivatives that in both cell lines exhibited a higher or at least equivalent pro-apoptotic effect than curcumin. The analysis of molecular mechanisms of action of the curcumin derivatives under study has highlighted that they decreased NF-κB transcriptional factor activity, and consequently the expression of some NF-κB targets. Our data confirmed once again that curcumin may represent a very good lead compound to design analogues with higher antitumor capacities and able to overcome drug resistance with respect to conventional ones, even in tumors difficult to treat as TNBC. MDPI 2019-10-26 /pmc/articles/PMC6958375/ /pubmed/31717764 http://dx.doi.org/10.3390/ph12040161 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Bonaccorsi, Paola Maria
Labbozzetta, Manuela
Barattucci, Anna
Salerno, Tania Maria Grazia
Poma, Paola
Notarbartolo, Monica
Synthesis of Curcumin Derivatives and Analysis of Their Antitumor Effects in Triple Negative Breast Cancer (TNBC) Cell Lines
title Synthesis of Curcumin Derivatives and Analysis of Their Antitumor Effects in Triple Negative Breast Cancer (TNBC) Cell Lines
title_full Synthesis of Curcumin Derivatives and Analysis of Their Antitumor Effects in Triple Negative Breast Cancer (TNBC) Cell Lines
title_fullStr Synthesis of Curcumin Derivatives and Analysis of Their Antitumor Effects in Triple Negative Breast Cancer (TNBC) Cell Lines
title_full_unstemmed Synthesis of Curcumin Derivatives and Analysis of Their Antitumor Effects in Triple Negative Breast Cancer (TNBC) Cell Lines
title_short Synthesis of Curcumin Derivatives and Analysis of Their Antitumor Effects in Triple Negative Breast Cancer (TNBC) Cell Lines
title_sort synthesis of curcumin derivatives and analysis of their antitumor effects in triple negative breast cancer (tnbc) cell lines
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958375/
https://www.ncbi.nlm.nih.gov/pubmed/31717764
http://dx.doi.org/10.3390/ph12040161
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