Portal de investigación
Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer
Fecha de publicación:
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Autores de INCLIVA
Grupos y Plataformas de I+D+i
Abstract
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 (IC50 values from 1.5 mu M to 58.4 mu M). 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.
This journal is © The Royal Society of Chemistry.
Datos de la publicación
- ISSN/ISSNe:
- 2632-8682, 2632-8682
- Tipo:
- Article
- Páginas:
- 2327-2341
- DOI:
- 10.1039/d3md00385j
- PubMed:
- 38020071
RSC Medicinal Chemistry ROYAL SOC CHEMISTRY
Citas Recibidas en Web of Science: 3
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Filiaciones
Financiación
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Cita
García A,Torres S,Vila L,Villarroel C,Bernabeu A,Eroles P,Cabedo N,Cortes D. Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer. RSC Med Chem. 2023. 14. (11):p. 2327-2341. IF:4,100. (2).
Synthesis of 2-aminopropyl benzopyran derivatives as potential agents against triple-negative breast cancer. García A, Torres S, Vila L, Villarroel C, Bernabeu A, Eroles P, Cabedo N et al. RSC Medicinal Chemistry. 2023 noviembre 15. 14 (11):2327-2341. DOI:10.1039/d3md00385j. PMID:38020071.
