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http://hdl.handle.net/10553/112583
Title: | Design and synthesis of naphthylchalcones as novel anti-leukaemia agents | Authors: | Leitão, Emília P.T. Ascenso, Osvaldo S. Santos de Almeida, Tania González, Ignacio Hernández, Inmaculada Quintana Aguiar, José Martín Estévez Rosas, Francisco Rijo, Patrícia |
UNESCO Clasification: | 32 Ciencias médicas 320101 Oncología 2302 Bioquímica 2306 Química orgánica |
Keywords: | Apoptosis Caspases Chalcones Claisen-Schmidt Condensation Flavanones, et al |
Issue Date: | 2021 | Journal: | Bioorganic Chemistry | Abstract: | A series of new hydroxylated chalcone derivatives with different substitution patterns on a phenyl ring A and B, were prepared by Claisen–Schmidt condensation in an aqueous alkaline base. The antiproliferative activity of the studied compounds was evaluated against the human leukaemia cell line U-937. The structure–activity relationship of these naphthylchalcones was investigated by the introduction of one methoxy or two methyl groups on the A ring, the introduction of a methoxy group on the naphthyl ring or by varying the position of the methoxy group on the A ring. The results revealed that the naphthylchalcone containing a methoxy group in position 6́ of the A ring was the most cytotoxic compound, with an IC50 value of 4.7 ± 0.5 μM against U-937 cells. This synthetic chalcone induced S and G2-M cell cycle arrest, a time-dependent increase in sub-G1 ratio and annexin-V positive cells, caspase activation and poly(ADP-ribose) polymerase cleavage. Apoptosis induction was blocked by a pan-caspase inhibitor and by the selective caspase-3/7 inhibitor and attenuated by the inhibition of c-jun N-terminal kinases / stress-activated protein kinases (JNK/SAPK) and phosphoinositide 3-kinase. The structure–activity relationship of naphthylchalcones against human leukaemia cells reveals that the major determining in cytotoxicity is the presence of a methoxy group in position 6́ of the A ring that suggest the potential of this compound or derivatives in the development of new anti-leukaemia drugs. | URI: | http://hdl.handle.net/10553/112583 | ISSN: | 0045-2068 | DOI: | 10.1016/j.bioorg.2021.105348 | Source: | Bioorganic Chemistry [ISSN 0045-2068], v. 117, 105348, (Diciembre 2021) |
Appears in Collections: | Artículos |
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