Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/116080
Título: Structure-activity relationships reveal a 2-furoyloxychalcone as a potent cytotoxic and apoptosis inducer for human U-937 and HL-60 leukaemia cells
Autores/as: Del Rosario García, Henoc 
Saavedra Díaz, Ester Gloria 
Brouard Martín,Ignacio 
González-Santana, Daniel
García, Celina
Spinola Lasso, Elena 
Tabraue Tarbay, Carlos 
Quintana Aguiar, José Martín 
Estévez Rosas, Francisco Jesús 
Clasificación UNESCO: 32 Ciencias médicas
2302 Bioquímica
Palabras clave: Apoptosis
Caspase
Cell Cycle
Chalcone
Cytotoxicity, et al.
Fecha de publicación: 2022
Publicación seriada: Bioorganic Chemistry 
Resumen: Synthetic flavonoids with new substitution patterns have attracted attention as potential anticancer drugs. Here, twelve chalcones were synthesized and their antiproliferative activities against five human tumour cells were evaluated. This series of chalcone derivatives was characterized by the presence of an additional aromatic or heterocyclic ring linked by an ether, in the case of a benzyl radical, or an ester or amide functional group in the case of a furoyl radical. In addition, the influence on cytotoxicity by the presence of one or three methoxy groups or a 2,4-dimethoxy-3-methyl system on the B ring of the chalcone scaffold was also explored. The results revealed that the most cytotoxic chalcones contain a furoyl substituent linked by an ester or an amide through the 2′-hydroxy or the 2′-amino group of the A ring of the chalcone skeleton, with IC50 values between 0.2 ± 0.1 μM and 1.3 ± 0.1 μM against human leukaemia cells. The synthetic chalcone 2′-furoyloxy-4-methoxychalcone (FMC) was, at least, ten-fold more potent than the antineoplastic agent etoposide against U-937 cells and displayed less cytotoxicity against human peripheral blood mononuclear cells. Treatment of U-937 and HL-60 cells with FMC induced cell cycle arrest at the G2-M phase, an increase in the percentage of sub-G1 and annexin-V positive cells, the release of mitochondrial cytochrome c, activation of caspase and poly(ADP-ribose) polymerase cleavage. In addition, it inhibited tubulin polymerization in vitro in a concentration dependent manner. Cell death triggered by this chalcone was decreased by the pan-caspase inhibitor z-VAD-fmk and was dependent of the generation of reactive oxygen species. We conclude that this furoyloxychalcone may be useful in the development of a potential anti-leukaemia strategy.
URI: http://hdl.handle.net/10553/116080
ISSN: 0045-2068
DOI: 10.1016/j.bioorg.2022.105926
Fuente: Bioorganic Chemistry [ISSN 0045-2068], v. 127, 105926, (Octubre 2022)
Colección:Artículos
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