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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
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.
ISSN: 0045-2068
DOI: 10.1016/j.bioorg.2021.105348
Source: Bioorganic Chemistry [ISSN 0045-2068], v. 117, 105348, (Diciembre 2021)
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