Please use this identifier to cite or link to this item: 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
Adobe PDF (1,7 MB)
Show full item record

SCOPUSTM   
Citations

2
checked on Oct 13, 2024

WEB OF SCIENCETM
Citations

2
checked on Oct 13, 2024

Page view(s)

82
checked on Aug 3, 2024

Download(s)

56
checked on Aug 3, 2024

Google ScholarTM

Check

Altmetric


Share



Export metadata



Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.