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Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer

Synthesis of three series of 2-aminopropyl derivatives containing a benzopyran nucleus was performed to evaluate their performance against triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-436) and normal breast epithelial cells (MCF10A). For the three series, the cytotoxic activity wa...

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Autores principales: García, Ainhoa, Torres-Ruiz, Sandra, Vila, Laura, Villarroel-Vicente, Carlos, Bernabeu, Álvaro, Eroles, Pilar, Cabedo, Nuria, Cortes, Diego
Formato: Online Artículo Texto
Lenguaje:English
Publicado: RSC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10650959/
https://www.ncbi.nlm.nih.gov/pubmed/38020071
http://dx.doi.org/10.1039/d3md00385j
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author García, Ainhoa
Torres-Ruiz, Sandra
Vila, Laura
Villarroel-Vicente, Carlos
Bernabeu, Álvaro
Eroles, Pilar
Cabedo, Nuria
Cortes, Diego
author_facet García, Ainhoa
Torres-Ruiz, Sandra
Vila, Laura
Villarroel-Vicente, Carlos
Bernabeu, Álvaro
Eroles, Pilar
Cabedo, Nuria
Cortes, Diego
author_sort García, Ainhoa
collection PubMed
description Synthesis of three series of 2-aminopropyl derivatives containing a benzopyran nucleus was performed to evaluate their performance against triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-436) and normal breast epithelial cells (MCF10A). For the three series, the cytotoxic activity was as follows: N-methylated derivatives (tertiary amines) 5b, 6b, and 7b > secondary amine benzopyrans 5, 6, and 7 > quaternary amine salts 5c, 6c, and 7c > free phenolic derivatives 5a, 6a, and 7a. The structure–activity relationship showed the importance of the presence of an amine group and a p-fluorobenzyloxy substituent in the chromanol ring (IC(50) values from 1.5 μM to 58.4 μM). In addition, 5a, 5b, 6a, and 7b displayed slight selectivity towards tumor cells. Compounds 5, 5a, 5b, 6, 6a, 6c, 7, and 7b showed apoptotic/necrotic effects due to, at least in part, an increase in reactive oxygen species generation, whereas 5b, 5c, 6b, 7a, and 7c caused cell cycle arrest in the G1 phase. Further cell-based mechanistic studies revealed that 5a, 6a, and 7b, which were the most promising compounds, downregulated the expression of Bcl-2, while 5b downregulated the expression of cyclins CCND1 and CCND2. Therefore, 2-aminopropyl benzopyran derivatives emerge as new hits and potential leads for developing useful agents against breast cancer.
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spelling pubmed-106509592023-10-04 Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer García, Ainhoa Torres-Ruiz, Sandra Vila, Laura Villarroel-Vicente, Carlos Bernabeu, Álvaro Eroles, Pilar Cabedo, Nuria Cortes, Diego RSC Med Chem Chemistry Synthesis of three series of 2-aminopropyl derivatives containing a benzopyran nucleus was performed to evaluate their performance against triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-436) and normal breast epithelial cells (MCF10A). For the three series, the cytotoxic activity was as follows: N-methylated derivatives (tertiary amines) 5b, 6b, and 7b > secondary amine benzopyrans 5, 6, and 7 > quaternary amine salts 5c, 6c, and 7c > free phenolic derivatives 5a, 6a, and 7a. The structure–activity relationship showed the importance of the presence of an amine group and a p-fluorobenzyloxy substituent in the chromanol ring (IC(50) values from 1.5 μM to 58.4 μM). In addition, 5a, 5b, 6a, and 7b displayed slight selectivity towards tumor cells. Compounds 5, 5a, 5b, 6, 6a, 6c, 7, and 7b showed apoptotic/necrotic effects due to, at least in part, an increase in reactive oxygen species generation, whereas 5b, 5c, 6b, 7a, and 7c caused cell cycle arrest in the G1 phase. Further cell-based mechanistic studies revealed that 5a, 6a, and 7b, which were the most promising compounds, downregulated the expression of Bcl-2, while 5b downregulated the expression of cyclins CCND1 and CCND2. Therefore, 2-aminopropyl benzopyran derivatives emerge as new hits and potential leads for developing useful agents against breast cancer. RSC 2023-10-04 /pmc/articles/PMC10650959/ /pubmed/38020071 http://dx.doi.org/10.1039/d3md00385j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
García, Ainhoa
Torres-Ruiz, Sandra
Vila, Laura
Villarroel-Vicente, Carlos
Bernabeu, Álvaro
Eroles, Pilar
Cabedo, Nuria
Cortes, Diego
Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer
title Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer
title_full Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer
title_fullStr Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer
title_full_unstemmed Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer
title_short Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer
title_sort synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10650959/
https://www.ncbi.nlm.nih.gov/pubmed/38020071
http://dx.doi.org/10.1039/d3md00385j
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